Sample records for cleavage fracture

  1. Elasto-viscoplastic phase field modelling of anisotropic cleavage fracture (United States)

    Shanthraj, P.; Svendsen, B.; Sharma, L.; Roters, F.; Raabe, D.


    A finite-strain anisotropic phase field method is developed to model the localisation of damage on a defined family of crystallographic planes, characteristic of cleavage fracture in metals. The approach is based on the introduction of an undamaged configuration, and the inelastic deformation gradient mapping this configuration to a damaged configuration is microstructurally represented by the opening of a set of cleavage planes in the three fracture modes. Crack opening is modelled as a dissipative process, and its evolution is thermodynamically derived. To couple this approach with a physically-based phase field method for brittle fracture, a scalar measure of the overall local damage is introduced, whose evolution is determined by the crack opening rates, and weakly coupled with the non-local phase field energy representing the crack opening resistance in the classical sense of Griffith. A finite-element implementation of the proposed model is employed to simulate the crack propagation path in a laminate and a polycrystalline microstructure. As shown in this work, it is able to predict the localisation of damage on the set of pre-defined cleavage planes, as well as the kinking and branching of the crack resulting from the crystallographic misorientation across the laminate boundary and the grain boundaries respectively.

  2. Method of Evaluating Delayed Fracture Susceptibility of Tempered Martensitic Steel Showing Quasi-Cleavage Fracture (United States)

    Matsumoto, Yu; Takai, Kenichi


    The difference in the hydrogen charging methods, immersion in a NH4SCN aqueous solution, and cathodic electrolysis in a NaOH aqueous solution, did not affect the hydrogen state present in the steel, but it did affect the surface state of the specimens through corrosion, causing fracture strength to fluctuate in tensile testes. As for stress application method, the fracture strength at lower crosshead speeds in tensile tests was consistent with that found for hydrogen precharging prior to stress application in CLTs as long as hydrogen charging was conducted by cathodic electrolysis. However, the fracture strength obtained with concurrent hydrogen charging without precharging prior to stress application in CLTs was higher than that with hydrogen precharging prior to stress application in CLTs regardless of the same hydrogen content. In other words, delayed fracture susceptibility was affected by the order of hydrogen charging and stress application for quasi-cleavage fracture associated with local plastic deformation, i.e., dislocation motion. Therefore, by taking into account the cathodic electrolysis in the NaOH solution, the low crosshead speed and the order of hydrogen charging and stress application, the fracture strength in CLTs, and tensile tests coincided with respect to quasi-cleavage fracture even though the stress application methods were different.


    Institute of Scientific and Technical Information of China (English)

    Francisco G.Emmerich; Alfredo G.Cunha; Carlos M.A.Girelli; Arnobio I.Vassem


    A characteristic of the fracture and cleavage experiments is that they are usually intrinsically destructive.Cracks do not completely heal in an unstressed system,even in crystals such as mica.Here,we used magnetic solids composed of magnetic strips for the non-destructive cleavage and brittle fracture experiments.Between the magnetic strips materials with different mechanical characteristics can be inserted,such as Teflon or foam strips,to change the mechanical properties of the solid.For the cleavage experiments,we developed an apparatus where parameters such as the main involved force can be measured easily.By inserting flaws,the magnetic solid can be used in dynamic fracture experiments,with the advantages of simulating macroscopically a non-destructive experiment in an easier way,that happen in real materials with much higher velocities.The apparatus and the used magnetic solid may be useful for demonstrations of fractures in classes.

  4. Microstructural parameters governing cleavage fracture behaviors in the ductile-brittle transition region in reactor pressure vessel steels

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Won-Jon; Lee, Bong-Sang; Oh, Yong-Jun; Huh, Moo-Young; Hong, Jun-Hwa


    The fracture behaviors in the ductile-brittle transition region of reactor pressure vessel (RPV) steels with similar chemical compositions but different manufacturing processes were examined in view of cleavage fracture stress at crack-tip. The steels typically had a variation in grain size and carbide size distribution through the different manufacturing processes. Fracture toughness was evaluated by using a statistical method in accordance to the ASTM standard E1921. From the fractography of the tested specimens, it was found that fracture toughness of the steels increased with increasing distance from the crack-tip to the cleavage initiating location, namely cleavage initiation distance (CID, X{sub f}) and its statistical mean value (K{sub JC(med)}) was proportional to the cleavage fracture stress ({sigma}{sub f}) determined from finite-element (FE) calculation at cleavage initiating location. On the other hand, {sigma}{sub f} could also be calculated by applying the size of microstructural parameters, such as carbide, grain and bainite packet, into the Griffith's theory for brittle fracture. Among the parameters, the {sigma}{sub f} obtained from the mean diameter of the carbides above 1% of the total population was in good agreement with the {sigma}{sub f} value from the FE calculation for the five different steels. The results suggest that the fracture toughness of bainitic RPV steels in the transition region is mostly influenced by only some 1% of total carbides and the critical step for cleavage fracture of the RPV steels should be the propagation of this carbide size crack to the adjacent ferrite matrix.

  5. Development of a Weibull model of cleavage fracture toughness for shallow flaws in reactor pressure vessel material

    Energy Technology Data Exchange (ETDEWEB)

    Bass, B.R.; Williams, P.T.; McAfee, W.J.; Pugh, C.E. [Oak Ridge National Lab., Heavy-Section Steel Technology Program, Oak Ridge, TN (United States)


    A primary objective of the United States Nuclear Regulatory Commission (USNRC) -sponsored Heavy-Section Steel Technology (HSST) Program is to develop and validate technology applicable to quantitative assessments of fracture prevention margins in nuclear reactor pressure vessels (RPVs) containing flaws and subjected to service-induced material toughness degradation. This paper describes an experimental/analytical program for the development of a Weibull statistical model of cleavage fracture toughness for applications to shallow surface-breaking and embedded flaws in RPV materials subjected to multi-axial loading conditions. The experimental part includes both material characterization testing and larger fracture toughness experiments conducted using a special-purpose cruciform beam specimen developed by Oak Ridge National Laboratory for applying biaxial loads to shallow cracks. Test materials (pressure vessel steels) included plate product forms (conforming to ASTM A533 Grade B Class 1 specifications) and shell segments procured from a pressurized-water reactor vessel intended for a nuclear power plant. Results from tests performed on cruciform specimens demonstrated that biaxial loading can have a pronounced effect on shallow-flaw fracture toughness in the lower-transition temperature region. A local approach methodology based on a three-parameter Weibull model was developed to correlate these experimentally-observed biaxial effects on fracture toughness. The Weibull model, combined with a new hydrostatic stress criterion in place of the more commonly used maximum principal stress in the kernel of the Weibull stress integral definition, is shown to provide a scaling mechanism between uniaxial and biaxial loading states for 2-dimensional flaws located in the A533-B plate material. The Weibull stress density was introduced as a matrice for identifying regions along a semi-elliptical flaw front that have a higher probability of cleavage initiation. Cumulative

  6. Further application of the cleavage fracture stress model for estimating the T{sub 0} of highly embrittled ferritic steels

    Energy Technology Data Exchange (ETDEWEB)

    Sreenivasan, P.R.


    The semi-empirical cleavage fracture stress model (CFS), based on the microscopic cleavage fracture stress, s{sub f}, for estimating the ASTM E1921 reference temperature (T{sub 0}) of ferritic steels from instrumented impact testing of unprecracked Charpy V-notch specimens is further confirmed by test results for additional steels, including steels highly embrittled by thermal aging or irradiation. In addition to the ferrite-pearlite, bainitic or tempered martensitic steels (which was examined earlier), acicular or polygonal ferrite, precipitation-strengthened or additional simulated heat affected zone steels are also evaluated. The upper limit for the applicability of the present CFS model seems to be T{sub 41J} ∝160 to 170 C or T{sub 0} or T{sub Qcfs} (T{sub 0} estimate from the present CFS model) ∝100 to 120 C. This is not a clear-cut boundary, but indicative of an area of caution where generation and evaluation of further data are required. However, the present work demonstrates the applicability of the present CFS model even to substantially embrittled steels. The earlier doubts expressed about T{sub Qcfs} becoming unduly non-conservative for highly embrittled steels has not been fully substantiated and partly arises from the necessity of modifications in the T{sub 0} evaluation itself at high degrees of embrittlement suggested in the literature.

  7. Confocal microscopy-fracture reconstruction and finite element modeling characterization of local cleavage toughness in a ferritic/martensitic steel in subsized Charpy V-notch impact tests

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, T. E-mail:; Odette, G.R.; Lucas, G.E.; Matsui, H


    The confocal microscopy (CM)-fracture reconstruction (FR) method, coupled with scanning electron microscopy (SEM) fractography, was used to measure the critical notch deformation conditions at cleavage initiation for two subsized Charpy V-notch (CVN) specimen geometries of Japan ferritic/martensitic steel (JFMS). A new method was developed to permit FR of notched specimens. Three-dimensional finite element analysis (FEA) simulations of the notch and specimen deformation were used to estimate values of critical micro-cleavage fracture stress, {sigma}{sup *}, and critical stressed area, A{sup *}. Since {sigma}{sup *}-A{sup *} is independent of size and geometry, it provides a fundamental local measure of cleavage toughness.

  8. Mechanisms and modeling of cleavage fracture in simulated heat-affected zone microstructures of a high-strength low alloy steel (United States)

    Lambert-Perlade, A.; Sturel, T.; Gourgues, A. F.; Besson, J.; Pineau, A.


    The effect of the welding cycle on the fracture toughness properties of high-strength low alloy (HSLA) steels is examined by means of thermal simulation of heat-affected zone (HAZ) microstructures. Tensile tests on notched bars and fracture toughness tests at various temperatures are performed together with fracture surface observations and cross-sectional analyses. The influence of martensite-austenite (M-A) constituents and of “crystallographic” bainite packets on cleavage fracture micromechanisms is, thus, evidenced as a function of temperature. Three weakest-link probabilistic models (the “Master-curve” (MC) approach, the Beremin model, and a “double-barrier” (DB) model) are applied to account for the ductile-to-brittle transition (DBT) fracture toughness curve. Some analogy, but also differences, are found between the MC approach and the Beremin model. The DB model, having nonfitted, physically based scatter parameters, is applied to the martensite-containing HAZ microstructures and gives promising results.

  9. Cleavage Fracture Modeling of Pressure Vessels under Transient Thermo-Mechanical Loading

    Energy Technology Data Exchange (ETDEWEB)

    Qian, Xudong [National University of Singapore; Dodds, Robert [University of Illinois; Yin, Shengjun [ORNL; Bass, Bennett Richard [ORNL


    The next generation of fracture assessment procedures for nuclear reactor pressure vessels (RPVs) will combine nonlinear analyses of crack-front response with stochastic treatments of crack size, shape, orientation, location, material properties and thermal-pressure transients. The projected computational demands needed to support stochastic approaches with detailed 3-D, nonlinear stress analyses of vessels containing defects appear well beyond current and near-term capabilities. In the interim, 2-D models become appealing to approximate certain classes of critical flaws in RPVs, and have computational demands within reach for stochastic frameworks. The present work focuses on the capability of 2-D models to provide values for the Weibull stress fracture parameter with accuracy comparable to those from very detailed 3-D models. Weibull stress approaches provide one route to connect nonlinear vessel response with fracture toughness values measured using small laboratory specimens. The embedded axial flaw located in the RPV wall near the cladding-vessel interface emerges from current linear-elastic, stochastic investigations as a critical contributor to the conditional probability of initiation. Three different types of 2-D models reflecting this configuration are subjected to a thermal-pressure transient characteristic of a critical pressurized thermal shock event. The plane-strain, 2-D models include: the modified boundary layer (MBL) model, the middle tension (M(T)) model, and the 2-D RPV model. The 2-D MBL model provides a high quality estimate for the Weibull stress but only in crack-front regions with a positive T-stress. For crack-front locations with low constraint (T-stress < 0), the M(T) specimen provides very accurate Weibull stress values but only for pressure load acting alone on the RPV. For RPVs under a combined thermal-pressure transient, Weibull stresses computed from the 2-D RPV model demonstrate close agreement with those computed from the

  10. Cleavage Fracture Modeling of Pressure Vessels Under Transient Thermo-Mechanical Loading

    Energy Technology Data Exchange (ETDEWEB)

    Qian, Xudong [National University of Singapore; Dodds, Robert [University of Illinois; Yin, Shengjun [ORNL; Bass, Bennett Richard [ORNL


    Abstract The next generation of fracture assessment procedures for nuclear reactor pressure vessels (RPVs) will combine nonlinear analyses of crack-front response with stochastic treatments of crack size, shape, orientation, location, material properties and thermal-pressure transients. The projected computational demands needed to support stochastic approaches with detailed 3-D, nonlinear stress analyses of vessels containing defects appear well beyond current and near-term capabilities. In the interim, 2-D models be-come appealing to approximate certain classes of critical flaws in RPVs, and have computational demands within reach for stochastic frameworks. The present work focuses on the capability of 2-D models to provide values for the Weibull stress fracture parameter with accuracy comparable to those from very detailed 3-D models. Weibull stress approaches provide one route to connect nonlinear vessel response with fracture toughness values measured using small laboratory specimens. The embedded axial flaw located in the RPV wall near the cladding-vessel interface emerges from current linear-elastic, stochastic investigations as a critical contributor to the conditional probability of initiation. Three different types of 2-D models reflecting this configuration are subjected to a thermal-pressure transient characteristic of a critical pressurized thermal shock event. The plane-strain, 2-D models include: the modified boundary layer (MBL) model, the middle tension (M(T)) model, and the 2-D RPV model. The 2-D MBL model provides a high quality estimate for the Weibull stress but only in crack-front regions with a positive T-stress. For crack-front locations with low constraint (T-stress < 0), the M(T) specimen provides very accurate Weibull stress values but only for pressure load acting alone on the RPV. For RPVs under a combined thermal-pressure transient, Weibull stresses computed from the 2-D RPV model demonstrate close agreement with those computed from

  11. Cleavage fracture and irradiation embrittlement of fusion reactor alloys: mechanisms, multiscale models, toughness measurements and implications to structural integrity assessment (United States)

    Odette, G. R.; Yamamoto, T.; Rathbun, H. J.; He, M. Y.; Hribernik, M. L.; Rensman, J. W.


    We describe the highly efficient master curves-shifts (MC-Δ T) method to measure and apply cleavage fracture toughness, KJc ( T), data and show that it is applicable to 9Cr martensitic steels. A reference temperature, T0, indexes the invariant MC shape on an absolute temperature scale. Then, T0 shifts (Δ T) are used to account for various effects of size and geometry, loading rate and irradiation embrittlement (Δ Ti). The paper outlines a multiscale model, relating atomic to structural scale fracture processes, that underpins the MC-Δ T method. At the atomic scale, we propose that the intrinsic microarrest toughness, Kμ( T), of the body-centered cubic ferrite lattice dictates an invariant shape of the macroscopic KJc ( T) curve. KJc ( T) can be modeled in terms of the true stress-strain ( σ- ɛ) constitutive law, σ ( T, ɛ), combined with a temperature-dependent critical local stress, σ*( T) and stressed volume, V*. The local fracture properties, σ*( T)- V*, are governed by coarse-scale brittle trigger particles and Kμ( T). Irradiation (and high strain rate) induced increases in the yield stress, Δ σy, lead to Δ Ti, with typical Δ Ti/Δ σy≈0.6±0.15 °C/MPa. However, Δ Ti associated with decreases in σ* and V* can result from a number of potential non-hardening embrittlement (NHE) mechanisms, including a large amount of He on grain boundaries. Estimates based on available data suggest that this occurs at >500-700 appm bulk He. Hardening and NHE are synergistic, and can lead to very large Δ Ti. NHE is signaled by large (>1 °C/MPa), or even negative, values of Δ Ti/Δ σy (for Δ σy1 and Δc/ Δy≫1. Indeed, in some circumstances, the benefits of irradiation due to increases in Pc may more than offset the liabilities of the decreases in Δc.

  12. Fracto—emissions in Catastrophic Cleavage Process

    Institute of Scientific and Technical Information of China (English)

    HonglaiTAN; WeiYANG


    Fracto-emissions accompanying crack propagation are observed in the recent experiments.The energy impulses during and after fracture stimulate the fracto-emissions.Model concerning atomic scale cleavage processes is proposed to formulate a catastrophic fracure theory relevant to these phenomena.A criterion for catastrophic jump of the cleavage potential is applied to representative crystals.

  13. Microstructure and cleavage in lath martensitic steels

    Directory of Open Access Journals (Sweden)

    John W Morris Jr, Chris Kinney, Ken Pytlewski and Y Adachi


    Full Text Available In this paper we discuss the microstructure of lath martensitic steels and the mechanisms by which it controls cleavage fracture. The specific experimental example is a 9Ni (9 wt% Ni steel annealed to have a large prior austenite grain size, then examined and tested in the as-quenched condition to produce a relatively coarse lath martensite. The microstructure is shown to approximate the recently identified 'classic' lath martensite structure: prior austenite grains are divided into packets, packets are subdivided into blocks, and blocks contain interleaved laths whose variants are the two Kurjumov–Sachs relations that share the same Bain axis of the transformation. When the steel is fractured in brittle cleavage, the laths in the block share {100} cleavage planes and cleave as a unit. However, cleavage cracks deflect or blunt at the boundaries between blocks with different Bain axes. It follows that, as predicted, the block size governs the effective grain size for cleavage.

  14. Cleavage crystallography of liquid metal embrittled aluminum alloys (United States)

    Reynolds, A. P.; Stoner, G. E.


    The crystallography of liquid metal-induced transgranular cleavage in six aluminum alloys having a variety of microstructures has been determined via Laue X-ray back reflection. The cleavage crystallography was independent of alloy microstructure, and the cleavage plane was 100-plane oriented in all cases. It was further determined that the cleavage crystallography was not influenced by alloy texture. Examination of the fracture surface indicated that there was not a unique direction of crack propagation. In addition, the existence of 100-plane cleavage on alloy 2024 fracture surfaces was inferred by comparison of secondary cleavage crack intersection geometry on the 2024 surfaces with the geometry of secondary cleavage crack intersections on the test alloys.

  15. Mezzo-scopic Analysis of Fracture Toughness in Steels

    Directory of Open Access Journals (Sweden)

    Miyata Takashi


    Full Text Available The cleavage fracture toughness of steels was mezzo-scopically analyzed on the basis of the statistical local fracture criterion approach. The statistical stress criterion at the crack tip region suggests that the cleavage fracture toughness in steels can be described as a function of the yield stress, the cleavage fracture stress, and other mechanical properties of the materials. Formulation of the cleavage fracture toughness was first examined through an investigation on correlation between the cleavage toughness and the cleavage fracture stress obtained in notched round bar specimens in accordance with the theoretical prediction. Then, the scatter of the toughness, specimen thickness effect on the toughness, deterioration of the toughness due to cold working and irradiation, and improvement of the toughness caused by the Ni addition, were analyzed through the formulation of the toughness.

  16. Fracture mechanics safety approaches

    Energy Technology Data Exchange (ETDEWEB)

    Roos, E.; Schuler, X.; Eisele, U. [Materials Testing Inst. (MPA), Univ. of Stuttgart (Germany)


    Component integrity assessments require the knowledge of reliable fracture toughness parameters characterising the initiation of the failure process in the whole relevant temperature range. From a large number of fracture mechanics tests a statistically based procedure was derived allowing to quantify the initiation of fracture toughness as a function of temperature as a closed function as well as the temperature dependence of the cleavage instability parameters. Alternatively to the direct experimental determination one also can use a correlation between fracture toughness and notch impact energy. (orig.)

  17. Mechanisms of intergranular fracture

    Energy Technology Data Exchange (ETDEWEB)

    Farkas, D. [Virginia Polytechnic Inst. and State Univ., Blacksburg, VA (United States). Dept. of Materials Science and Engineering


    The authors present a study of the atomistic mechanisms of crack propagation along grain boundaries in metals and alloys. The failure behavior showing cleavage crack growth and/or crack-tip dislocation emission is demonstrated using atomistic simulations for an embedded-atom model. The simulations follow the quasi-equilibrium growth of a crack as the stress intensity applied increases. Dislocations emitted from crack tips normally blunt the crack and inhibit cleavage, inducing ductile behavior. When the emitted dislocations stay near the crack tip (sessile dislocations), they do blunt the crack but brittle cleavage can occur after the emission of a sufficient number of dislocations. The fracture process occurs as a combination of dislocation emission/micro-cleavage portions that are controlled by the local atomistic structure of the grain boundary. The grain boundary is shown to be a region where dislocation emission is easier, a mechanism that competes with the lower cohesive strength of the boundary region.

  18. IUTAM Symposium on Nonlinear Analysis of Fracture (United States)


    approach has been extended by Koers et al. (1995) and Xia and Shih (1996) to take full account of the ductile crack growth prior to cleavage...Society for Testing and Materials, Philadelphia. Koers , R.W.J., Krom, A.H.M. and Bakker, A. (1995) Prediction of Cleavage Fracture in the Brittle to

  19. A cleavage toughness master curve model (United States)

    Odette, G. R.; He, M. Y.


    Development of fusion power will require a fracture toughness database, derived largely from small specimen tests, closely integrated with methods to assess first wall and blanket structural integrities. A master curve-shift (MC-ΔT) method has been proposed as an engineering expedient to treat the effects of structural geometry, irradiation, loading rates and safety margins. However, a number of issues related to the MC-ΔT method remain to be resolved, including the universality of MC shapes. A new micromechanical model of fracture toughness in the cleavage transition regime is proposed that combines analytical representations of finite element analysis simulations of crack-tip stress fields with a local critical stress-critical stressed area (σ∗-A∗) fracture criterion. This model, has been successful in predicting geometry effects, as well as high loading rate and irradiation hardening-induced Charpy shifts. By incorporating a modest temperature dependence in σ∗(T), an inconsistency between model predictions and an observed universal-type MC shape is resolved.

  20. Fracture Phenomena in Amorphous Selenium

    DEFF Research Database (Denmark)

    Lindegaard-Andersen, Asger; Dahle, Birgit


    the velocities of ultrasonic longitudinal and shear waves were measured to 1820 m/sec and 930 m/sec, respectively. Based on these results the two line systems in the transition zone can be interpreted as ``Wallner lines'' with sources within the zone. ©1966 The American Institute of Physics......Fracture surfaces of amorphous selenium broken in flexure at room temperature have been studied. The fracture velocity was found to vary in different regions of the fracture surface. Peculiar features were observed in a transition zone between fast and slower fracture. In this zone cleavage steps...

  1. Fracture in sintered Sm-Co permanent magnetic materials

    Institute of Scientific and Technical Information of China (English)

    LI; Anhua(李安华); DONG; Shengzhi(董生智); LI; Wei(李卫)


    The bending strength and fracture toughness of sintered Sm-Co permanent magnetic materials are measured. A scanning electron microscope equipped with an energy dispersive X-ray analysis system is employed to investigate the bending fractography. The fracture behavior and micromechanism are discussed. The fracture behavior of sintered Sm-Co permanent magnetic materials exhibits cleavage fracture. Some Sm-rich impurities are found in fracture plane, suggesting that the Sm-rich impurities help reduce the cleavage brittleness of sintered Sm-Co permanent magnetic materials. The possible methods for improving the strength and toughness are also proposed.

  2. Effects of Magnetic Field on Fracture of Al-Li Alloy Containing Cerium

    Institute of Scientific and Technical Information of China (English)

    刘兵; 王西宁; 陈铮


    The effects of magnetic field on fracture feature and microstructure of Al-Li alloys containing Ce were investigated. Experiment results show that the fracture features and the microstructures are changed with the magnetic field. The fracture surface of the alloys is mainly quasi-cleavage without applying magnetic field. With a magnetic field, the fracture of quasi-cleavage changes to more secondary cracks and less quasi-cleavage plates on fracture surface. Grains become thinner and uniform with applying magnetic field. The influence of magnetic field on atom diffusion was discussed.

  3. Centralspindlin in Rappaport's cleavage signaling. (United States)

    Mishima, Masanori


    Cleavage furrow in animal cell cytokinesis is formed by cortical constriction driven by contraction of an actomyosin network activated by Rho GTPase. Although the role of the mitotic apparatus in furrow induction has been well established, there remain discussions about the detailed molecular mechanisms of the cleavage signaling. While experiments in large echinoderm embryos highlighted the role of astral microtubules, data in smaller cells indicate the role of central spindle. Centralspindlin is a constitutive heterotetramer of MKLP1 kinesin and the non-motor CYK4 subunit and plays crucial roles in formation of the central spindle and recruitment of the downstream cytokinesis factors including ECT2, the major activator of Rho during cytokinesis, to the site of division. Recent reports have revealed a role of this centralspindlin-ECT2 pathway in furrow induction both by the central spindle and by the astral microtubules. Here, a unified view of the stimulation of cortical contractility by this pathway is discussed. Cytokinesis, the division of the whole cytoplasm, is an essential process for cell proliferation and embryonic development. In animal cells, cytokinesis is executed using a contractile network of actin filaments driven by a myosin-II motor that constricts the cell cortex (cleavage furrow ingression) into a narrow channel between the two daughter cells, which is resolved by scission (abscission) [1-3]. The anaphase-specific organization of the mitotic apparatus (MA, spindle with chromosomes plus asters) positions the cleavage furrow and plays a major role in spatial coupling between mitosis and cytokinesis [4-6]. The nucleus and chromosomes are dispensable for furrow specification [7-10], although they contribute to persistent furrowing and robust completion in some cell types [11,12]. Likewise, centrosomes are not essential for cytokinesis, but they contribute to the general fidelity of cell division [10,13-15]. Here, classical models of cleavage furrow

  4. [Atlas fractures]. (United States)

    Schären, S; Jeanneret, B


    Fractures of the atlas account for 1-2% of all vertebral fractures. We divide atlas fractures into 5 groups: isolated fractures of the anterior arch of the atlas, isolated fractures of the posterior arch, combined fractures of the anterior and posterior arch (so-called Jefferson fractures), isolated fractures of the lateral mass and fractures of the transverse process. Isolated fractures of the anterior or posterior arch are benign and are treated conservatively with a soft collar until the neck pain has disappeared. Jefferson fractures are divided into stable and unstable fracture depending on the integrity of the transverse ligament. Stable Jefferson fractures are treated conservatively with good outcome while unstable Jefferson fractures are probably best treated operatively with a posterior atlanto-axial or occipito-axial stabilization and fusion. The authors preferred treatment modality is the immediate open reduction of the dislocated lateral masses combined with a stabilization in the reduced position using a transarticular screw fixation C1/C2 according to Magerl. This has the advantage of saving the atlanto-occipital joints and offering an immediate stability which makes immobilization in an halo or Minerva cast superfluous. In late instabilities C1/2 with incongruency of the lateral masses occurring after primary conservative treatment, an occipito-cervical fusion is indicated. Isolated fractures of the lateral masses are very rare and may, if the lateral mass is totally destroyed, be a reason for an occipito-cervical fusion. Fractures of the transverse processes may be the cause for a thrombosis of the vertebral artery. No treatment is necessary for the fracture itself.

  5. Experimental study about nano-deformation field near quasi-cleavage crack tip

    Institute of Scientific and Technical Information of China (English)

    邢永明; 戴福隆; 杨卫FML


    Using the nano-moire method, we measure the near tip nanoscopic deformation on the {111 } plane of single crystal silicon with a loaded quasi-cleavage crack running in the [110] direction. The measured strain distribution ahead of the crack tip agrees with the linear elastic fracture mechanics prediction up to 10 nm from the crack tip. Dislocations of Peierls type are detected and they extend from the crack tip over a length of hundreds of Burgers vectors.

  6. Fracture behaviour of polycrystalline tungsten (United States)

    Gaganidze, Ermile; Rupp, Daniel; Aktaa, Jarir


    Fracture behaviour of round blank polycrystalline tungsten was studied by means of three point bending Fracture-Mechanical (FM) tests at temperatures between RT and 1000 °C and under high vacuum. To study the influence of the anisotropic microstructure on the fracture toughness (FT) and ductile-to-brittle transition (DBT) the specimens were extracted in three different, i.e. longitudinal, radial and circumferential orientations. The FM tests yielded distinctive fracture behaviour for each specimen orientation. The crack propagation was predominantly intergranular for longitudinal orientation up to 600 °C, whereas transgranular cleavage was observed at low test temperatures for radial and circumferentially oriented specimens. At intermediate test temperatures the change of the fracture mode took place for radial and circumferential orientations. Above 800 °C all three specimen types showed large ductile deformation without noticeable crack advancement. For longitudinal specimens the influence of the loading rate on the FT and DBT was studied in the loading rate range between 0.06 and 18 MPa m1/2/s. Though an increase of the FT was observed for the lowest loading rate, no resolvable dependence of the DBT on the loading rate was found partly due to loss of FT validity. A Master Curve approach is proposed to describe FT vs. test temperature data on polycrystalline tungsten. Fracture safe design space was identified by analysis compiled FT data.

  7. Hip fracture - discharge (United States)

    Inter-trochanteric fracture repair - discharge; Subtrochanteric fracture repair - discharge; Femoral neck fracture repair - discharge; Trochanteric fracture repair - discharge; Hip pinning surgery - discharge

  8. Ab initio-based fracture toughness estimates and transgranular traction-separation modelling of zirconium hydrides (United States)

    Olsson, P. A. T.; Kese, K.; Kroon, M.; Alvarez Holston, A.-M.


    In this work we report the results of an ab initio study of the transgranular fracture toughness and cleavage of brittle zirconium hydrides. We use the Griffith-Irwin relation to assess the fracture toughness using calculated surface energy and estimated isotropic Voigt-Reuss-Hill averages of the elastic constants. The calculated fracture toughness values are found to concur well with experimental data, which implies that fracture is dominated by cleavage failure. To investigate the cleavage energetics, we model the decohesion process. To describe the interplanar interaction we adopt Rose’s universal binding energy relation, which is found to reproduce the behaviour accurately. The modelling shows that the work of fracture and ductility decreases with increasing hydrogen content.

  9. [Acetabular fractures]. (United States)

    Gänsslen, A; Oestern, H J


    Treatment of acetabular fractures requires extensive knowledge of the bony anatomy, the amount of possible exposure of the bone with the selected approaches and fracture type-dependent indications of operative treatment. Classification of the fracture with detailed analysis of the fracture morphology is the basis for decision making and planning. The primary treatment aim is the anatomic reconstruction of the acetabulum which results in optimal long-term results.The basis of this overview is the presentation of standard treatment concepts in acetabular fracture surgery. Beside characteristics of the acetabular bony anatomy, biomechanical and pathomechanical principles and the relevant radiological anatomy, the treatment options, both conservative and operative and basic principles of the indications for standard surgical approaches will be discussed.The special fracture type is discussed in detail regarding incidence, injury mechanism, concomitant injuries, options for conservative and operative treatment, quality of operative reduction and long-term results.Furthermore, epidemiological data on typical postoperative complications are evaluated.

  10. Sports fractures.


    DeCoster, T. A.; Stevens, M. A.; Albright, J. P.


    Fractures occur in athletes and dramatically influence performance during competitive and recreational activities. Fractures occur in athletes as the result of repetitive stress, acute sports-related trauma and trauma outside of athletics. The literature provides general guidelines for treatment as well as a variety of statistics on the epidemiology of fractures by sport and level of participation. Athletes are healthy and motivated patients, and have high expectations regarding their level o...

  11. Dataset of cocoa aspartic protease cleavage sites

    Directory of Open Access Journals (Sweden)

    Katharina Janek


    Full Text Available The data provide information in support of the research article, “The cleavage specificity of the aspartic protease of cocoa beans involved in the generation of the cocoa-specific aroma precursors” (Janek et al., 2016 [1]. Three different protein substrates were partially digested with the aspartic protease isolated from cocoa beans and commercial pepsin, respectively. The obtained peptide fragments were analyzed by matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF-MS/MS and identified using the MASCOT server. The N- and C-terminal ends of the peptide fragments were used to identify the corresponding in-vitro cleavage sites by comparison with the amino acid sequences of the substrate proteins. The same procedure was applied to identify the cleavage sites used by the cocoa aspartic protease during cocoa fermentation starting from the published amino acid sequences of oligopeptides isolated from fermented cocoa beans.

  12. Limited caspase cleavage of human BAP31. (United States)

    Määttä, J; Hallikas, O; Welti, S; Hildén, P; Schröder, J; Kuismanen, E


    Human BAP31 was cleaved at both of its two identical caspase cleavage sites in two previously reported models of apoptosis. We show here that only the most carboxy-terminal site is cleaved during apoptosis induced in HeLa cells by tunicamycin, tumor necrosis factor and cycloheximide, or staurosporine. Similar results were obtained in HL-60 cells using Fas/APO-1 antibodies, or cycloheximide. This limited cleavage, which is inhibited by several caspase inhibitors, removes eight amino acids from human BAP31 including the KKXX coat protein I binding motif. Ectopic expression of the resulting cleavage product induces redistribution of mannosidase II from the Golgi and prevents endoplasmic reticulum to Golgi transport of virus glycoproteins.

  13. Fracture Mechanics

    CERN Document Server

    Zehnder, Alan T


    Fracture mechanics is a vast and growing field. This book develops the basic elements needed for both fracture research and engineering practice. The emphasis is on continuum mechanics models for energy flows and crack-tip stress- and deformation fields in elastic and elastic-plastic materials. In addition to a brief discussion of computational fracture methods, the text includes practical sections on fracture criteria, fracture toughness testing, and methods for measuring stress intensity factors and energy release rates. Class-tested at Cornell, this book is designed for students, researchers and practitioners interested in understanding and contributing to a diverse and vital field of knowledge. Alan Zehnder joined the faculty at Cornell University in 1988. Since then he has served in a number of leadership roles including Chair of the Department of Theoretical and Applied Mechanics, and Director of the Sibley School of Mechanical and Aerospace Engineering.  He teaches applied mechanics and his research t...

  14. Crack branching in carbon steel. Fracture mechanisms (United States)

    Syromyatnikova, A. S.; Alekseev, A. A.; Levin, A. I.; Lyglaev, A. V.


    The fracture surfaces of pressure vessels made of carbon steel that form during crack branching propagation are examined by fractography. Crack branching is found to occur at a crack velocity higher than a certain critical value V > V c . In this case, the material volume that is involved in fracture and depends on the elastoplastic properties of the material and the sample width has no time to dissipate the energy released upon crack motion via the damage mechanisms intrinsic in the material under given deformation conditions (in our case, via cracking according to intragranular cleavage).

  15. Cleavage site analysis in picornaviral polyproteins

    DEFF Research Database (Denmark)

    Blom, Nikolaj; Hansen, Jan; Blaas, Dieter;


    are indeed cleaved awaits experimental verification. Additionally, we report several errors detected in the protein databases. A computer server for prediction of cleavage sites by picornaviral proteinases is publicly available at the e-mail address or via WWW at

  16. Initiation of cleavage in a low alloy steel: effect of a ductile damage localized around inclusions; Declenchement du clivage dans un acier faiblement allie: role de l'endommagement ductile localise autour des inclusions

    Energy Technology Data Exchange (ETDEWEB)

    Carassou, S


    The fracture mechanism in a low alloy steel, used in the pressurised water reactor vessel, has been studied in the ductile to brittle transition temperature range. We used the local approach of fracture in conjunction with both fractographic observations and numerical simulations. Previous studies suggested the onset of cleavage to be favoured by the presence of nearby manganese sulphide (MnS) clusters: the ductile damaged zone localised inside a cluster increases the stress around it, and so contribute to the triggering of cleavage due to nearby classical sites, like carbides. The experimental study of size dependence and anisotropy on the global fracture behaviour, together with fractographic observations, give here the proof of the influence of MnS clusters on the onset of cleavage in this steel. Fracture behaviour of pre-cracked specimens tested in the transition regime has then been simulated, by three dimensional finite element method computations. Ductile tearing process preceding the cleavage onset at those temperatures regime was well reproduced by the Rousselier's model. Failure probabilities, related to given stress states, has been given by post-processor calculations, using a probabilistic model based on the specific cleavage fracture process. Fracture toughness scatter of the steel, tested in the transition regime, is then well reproduced by those calculations. However, the critical cleavage stress of an elementary volume, that scales for the fracture process, is still assumed to be temperature dependant. Numerical simulations of the local fracture process suggest that this temperature effect can partly be explained by the temperature dependant decrease of the stress amplification due to the MnS clusters. (author)

  17. Fracture mechanics

    CERN Document Server

    Perez, Nestor


    The second edition of this textbook includes a refined presentation of concepts in each chapter, additional examples; new problems and sections, such as conformal mapping and mechanical behavior of wood; while retaining all the features of the original book. The material included in this book is based upon the development of analytical and numerical procedures pertinent to particular fields of linear elastic fracture mechanics (LEFM) and plastic fracture mechanics (PFM), including mixed-mode-loading interaction. The mathematical approach undertaken herein is coupled with a brief review of several fracture theories available in cited references, along with many color images and figures. Dynamic fracture mechanics is included through the field of fatigue and Charpy impact testing. Explains computational and engineering approaches for solving crack-related problems using straightforward mathematics that facilitate comprehension of the physical meaning of crack growth processes; Expands computational understandin...

  18. Hip Fracture (United States)

    ... Medicine. 2014;161:189. Lewiecki EM. Prevention of osteoporosis. Accessed Dec. 31, 2014. Hip fractures among older adults. Centers for Disease Control and Prevention. http://www. ...

  19. Fracture mechanics (United States)

    Shannon, John L., Jr.


    The application of fracture mechanics to the design of ceramic structures will require the precise measurement of crack growth and fracture resistance of these materials over their entire range of anticipated service temperatures and standardized test methods for making such measurements. The development of a standard test for measuring the plane strain fracture toughness is sought. Stress intensity factor coefficients were determined for three varieties of chevron-notch specimens, and fracture toughness measurements were made on silicon nitrides, silicon carbides, and aluminum oxides to assess the performance of each specimen variety. It was determined that silicon nitride and silicon carbides have flat crack growth resistance curves, but aluminum oxide does not. Additionally, batch-to-batch differences were noticed for the aluminum oxide. Experiments are continuing to explain the rising crack growth resistance and batch-to-batch variations for the aluminum oxide.

  20. Analysis of fracture toughness in transition temperature region of a Mn-Mo-Ni low-alloy steel

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Ho; Hwang, Byoung Chul; Lee, Sung Hak [Pohang Univ. of Science and Technology, Pohang (Korea, Republic of)


    This study is concerned with the analysis of fracture toughness in the transition region of a Mn-Mo-Ni low-alloy steel according to ASTM E1921 standard test method. Elastic-plastic cleavage fracture toughness, K{sub Jc} was determined by 3-point bend tests, using precracked Charpy V-notch (PCVN) specimens, and then the measured K{sub Jc} values were interpreted by the 3-parameter Weibull distribution with a theoretical slope of 4. fractographic observation indicated that the critical distance from a precrack tip to a cleavage initiation site linearly increased with increasing the critical J(J{sub c}) value, and that the stretch zone width had a good correlation with K{sub Jc} value, irrespective of testing temperature. Relationship between J{sub c} and critical distance, local fracture stress, and plane strain fracture toughness were discussed on the basis of the cleavage fracture behavior in the transition temperature region.

  1. Regioselectivity in the Reductive Bond Cleavage of Diarylalkylsulfonium Salts

    DEFF Research Database (Denmark)

    Kampmeier, Jack; Mansurul Hoque, AKM; D. Saeva, Franklin;


    This investigation was stimulated by reports that one-electron reductions of monoaryldialkylsulfonium salts never give aryl bond cleavage whereas reductions of diarylmonoalkylsulfonium salts preferentially give aryl bond cleavage. We studied the product ratios from the reductive cleavage of di-4-...

  2. The cleavage of phosphoenolpyruvate by vanadate. (United States)

    Aureliano, M; Leta, J; Madeira, V M; de Meis, L


    Vanadate rapidly promotes the cleavage of phosphoenolpyruvate with phosphate liberation. This was not observed when ATP, glucose-6-phosphate and acetyl phosphate were incubated with vanadate. 51V NMR spectra shows that phosphoenolpyruvate and acetyl phosphate broadened and shifted upfield the monomeric vanadate signal at -561 ppm, indicative of vanadate/phosphate interactions. Comparatively, smaller changes were detected when glucose-6-phosphate was added to the vanadate solution. The shift behavior was not observed in the presence of ATP, ADP or pyruvate.

  3. In vivo analysis of the Notch receptor S1 cleavage.

    Directory of Open Access Journals (Sweden)

    Robert J Lake

    Full Text Available A ligand-independent cleavage (S1 in the extracellular domain of the mammalian Notch receptor results in what is considered to be the canonical heterodimeric form of Notch on the cell surface. The in vivo consequences and significance of this cleavage on Drosophila Notch signaling remain unclear and contradictory. We determined the cleavage site in Drosophila and examined its in vivo function by a transgenic analysis of receptors that cannot be cleaved. Our results demonstrate a correlation between loss of cleavage and loss of in vivo function of the Notch receptor, supporting the notion that S1 cleavage is an in vivo mechanism of Notch signal control.

  4. SVM-based prediction of caspase substrate cleavage sites

    Directory of Open Access Journals (Sweden)

    Ranganathan Shoba


    Full Text Available Abstract Background Caspases belong to a class of cysteine proteases which function as critical effectors in apoptosis and inflammation by cleaving substrates immediately after unique sites. Prediction of such cleavage sites will complement structural and functional studies on substrates cleavage as well as discovery of new substrates. Recently, different computational methods have been developed to predict the cleavage sites of caspase substrates with varying degrees of success. As the support vector machines (SVM algorithm has been shown to be useful in several biological classification problems, we have implemented an SVM-based method to investigate its applicability to this domain. Results A set of unique caspase substrates cleavage sites were obtained from literature and used for evaluating the SVM method. Datasets containing (i the tetrapeptide cleavage sites, (ii the tetrapeptide cleavage sites, augmented by two adjacent residues, P1' and P2' amino acids and (iii the tetrapeptide cleavage sites with ten additional upstream and downstream flanking sequences (where available were tested. The SVM method achieved an accuracy ranging from 81.25% to 97.92% on independent test sets. The SVM method successfully predicted the cleavage of a novel caspase substrate and its mutants. Conclusion This study presents an SVM approach for predicting caspase substrate cleavage sites based on the cleavage sites and the downstream and upstream flanking sequences. The method shows an improvement over existing methods and may be useful for predicting hitherto undiscovered cleavage sites.

  5. Galeazzi fracture. (United States)

    Atesok, Kivanc I; Jupiter, Jesse B; Weiss, Arnold-Peter C


    Galeazzi fracture is a fracture of the radial diaphysis with disruption at the distal radioulnar joint (DRUJ). Typically, the mechanism of injury is forceful axial loading and torsion of the forearm. Diagnosis is established on radiographic evaluation. Underdiagnosis is common because disruption of the ligamentous restraints of the DRUJ may be overlooked. Nonsurgical management with anatomic reduction and immobilization in a long-arm cast has been successful in children. In adults, nonsurgical treatment typically fails because of deforming forces acting on the distal radius and DRUJ. Open reduction and internal fixation is the preferred surgical option. Anatomic reduction and rigid fixation should be followed by intraoperative assessment of the DRUJ. Further intraoperative interventions are based on the reducibility and postreduction stability of the DRUJ. Misdiagnosis or inadequate management of Galeazzi fracture may result in disabling complications, such as DRUJ instability, malunion, limited forearm range of motion, chronic wrist pain, and osteoarthritis.

  6. Fracture Blisters

    Directory of Open Access Journals (Sweden)

    Uebbing, Claire M


    Full Text Available Fracture blisters are a relatively uncommon complication of fractures in locations of the body, such as the ankle, wrist elbow and foot, where skin adheres tightly to bone with little subcutaneous fat cushioning. The blister that results resembles that of a second degree burn.These blisters significantly alter treatment, making it difficult to splint or cast and often overlying ideal surgical incision sites. Review of the literature reveals no consensus on management; however, most authors agree on early treatment prior to blister formation or delay until blister resolution before attempting surgical correction or stabilization. [West J Emerg Med. 2011;12(1;131-133.

  7. Rib Fractures (United States)

    ... Commentary Recent News Scientists Working on Solar-Powered Prosthetic Limbs Exercise a Great Prescription to Help Older Hearts Bavencio Approved for Rare Skin Cancer Older Mothers May Raise Better-Behaved Kids, Study ... or a collapsed lung (pneumothorax—see Traumatic Pneumothorax ). An injury that fractures the lower ribs sometimes also damages the liver (see Liver ...

  8. Fracture source

    Directory of Open Access Journals (Sweden)


    Full Text Available The fracture properties of many different types of fibers are covered in a timely new book that will prove to be a tremendous source of information and references for researchers in the wide and diverse field of fibers and composites, says Bill Clegg.

  9. Abyssal fiction: common shares, colonial cleavages

    Directory of Open Access Journals (Sweden)

    Alexandre Montaury


    Full Text Available The paper aims to develop a reflection on the interaction between the legacies of colonialism and traditional symbolic and cultural practices in African Portuguese-speaking spaces. From a preliminary analysis of fictional texts of wide circulation in Brazil, aims to examine the cleavages, or “abyssal lines” that constitute experiences printed in the daily life of the former Portuguese colony of Cape Verde, Mozambique and Angola.---DOI:

  10. Effects of grain size on fracture toughness in transition temperature region of Mn-Mo-Ni low-alloy steels

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sangho; Lee, Sunghak; Lee, Bong Sang


    An investigation was conducted into the effect of grain size on fracture toughness in the transition temperature region of Mn-Mo-Ni low-alloy steels used for nuclear pressure vessels. Three kinds of steels with different austenite grain sizes (AGS) were fabricated by varying the contents of Al and N, and their microstructures and mechanical properties were examined. Elastic-plastic cleavage fracture toughness, K{sub Jc}, was determined by three-point bend tests of precracked Charpy V-notch (PCVN) specimens according to ASTM E1921 standard test method. When the AGS decreased, the total number of carbides increased, while the size and the aspect ratio of carbides decreased. Local fracture stresses, estimated from a theoretical stress distribution in front of a crack tip, were found to be mainly determined by the 92nd% size of carbides. Cross-sectional areas beneath fracture surfaces were observed to understand microstructural features to affect the cleavage crack propagation behavior. The results showed that measured cleavage fracture units were smaller than AGSs, indicating that packet boundaries as well as austenite grain boundaries played an important role in the cleavage crack propagation. Based on the electron back-scatter diffraction (EBSD) results, the cleavage fracture units could also be matched with the effective grain sizes determined by the misorientation tolerance angle of 25 deg.

  11. Relationship between grain size and fracture toughness in transition region of Mn-Mo-Ni low-alloy steels

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Ho; Lee, Sung Hak [Pohang Univ. of Science and Technology, Pohang (Korea, Republic of); Oh, Yong Jun [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)


    The present study aims at interpreting the effect of grain size on fracture toughness in the transition region of Mn-Mo-Ni low-alloy steels. Three kinds of steels with different austenite grain sizes were fabricated, and their microstructures and mechanical properties were examined. Elastic-plastic cleavage fracture toughness, K{sub Jc}, was determined by 3-point bend tests of precracked Charpy V-notch (PCVN) specimens according to ASTM E1921 standard test method. When the austenite grain size decreased, the total number of carbides increased, while the size and the aspect ratio of carbides decreased. Local fracture stresses, estimated from a theoretical stress distribution in front of a crack tip, were found to be mainly determined by the 92%th size of carbides. Cross-sectional areas beneath fracture surfaces were observed to understand microstructural features to affect the cleavage crack propagation behavior. The results showed that measured cleavage fracture units were smaller than austenite grain sizes, indicating that packet boundaries as well as austenite grain boundaries played an important role in the cleavage crack propagation. Based on the electron back-scatter diffraction (EBSD) results, the cleavage fracture units could also be matched with the effective grain sizes determined by the misorientation tolerance angle of 25 degree.

  12. Intratree Variability of Cleavage Resistance of Chinese Fir from Plantation

    Institute of Scientific and Technical Information of China (English)

    XU Ming; REN Haiqing; LUO Xiuqin; YIN Yafang


    This paper studied the variation of cleavage resistance of Chinese fir wood from plantation.Six trees of 36 years old were investigated,and the cleavage resistance properties for 672 samples made of the trees were tested.The samples were cut from the sapwood and heartwood at different directions (south and north) and heights (1.3,3.3,5.3 and 7.3 m) of the trees.The result showed that:tangential cleavage resistance was higher than radial one, and cleavage resistance of sapwood was higher than that of heartwood,but there was no significant difference in cleavage resistances between sections of the north and the south of the trees.There was a little variation in cleavage resistance between the radial and tangential from butt to top log,which shows alittle decrease with the height from 1.3 to 5.3 m,but a rise in the top of the trees.

  13. Presence of Meiotic Spindles Indicates Early Cleavage of Embryos

    Institute of Scientific and Technical Information of China (English)


    Objective To assess whether the detection of the meiotic spindle could anticipate the appearance of early cleavage.Methods Oocytes were obtained from stimulated ovaries of consenting patients undergoing oocytes retrieval for ICSI.Spindles were imaged with the Polscope.After ICSI,oocytes with or without spindles were cultured for examination of early cleavage and embryo development.A total of 328 oocytes from 50 cycles were examined with the Polscope and inseminated by ICSI.Results Spindles were imaged in 81.7% of oocytes.After ICSI,more oocytes with spindles (78.4%) fertilized normally than oocytes without spindles (53.3%)(P<0.001).At 25-27 h post ICSI.more fertilized oocytes developed from oocytes with spindles (81.9%) were detected early cleavage than those from oocytes without spindles(28.1%)(P<0.001).Significantly more embryos with early cleavage (82.2%) developed to high quality embryos at d 3 compared with the embryos without early cleavage(48.3%)(P=0.001).The value of rs related to the relationship between spindles and early cleavage was 0.420(P<0.0001).Conclusion The existing of the early cleavage may have a predictive value on the opportunity of high quality embryos and the existing of the spindle may have a predictive value in the appearance of early cleavage.

  14. Tibia (Shinbone) Shaft Fractures (United States)

    .org Tibia (Shinbone) Sha Fractures Page ( 1 ) The tibia, or shinbone, is the most common fractured long bone in ... body. The long bones include the femur, humerus, tibia, and fibula. A tibial sha fracture occurs along ...

  15. Growth Plate Fractures (United States)

    ... the most widely used by doctors is the Salter-Harris system, described below. Type I Fractures These ... incidence of growth plate fractures peaks in adolescence. Salter-Harris classification of growth plate fractures. AAOS does ...

  16. Chopart fractures. (United States)

    Klaue, Kaj


    The Chopart articular space was described by François Chopart (1743-1795) as a practical space for amputations in cases of distal foot necrosis. It corresponds to the limit between the anatomical hind-foot and the mid-foot. The bones involved are the talus and the calcaneus proximally, and the navicular and the cuboid distally. This space thus holds two functionally distinct entities, the anterior part of the coxa pedis (an essential functional joint) and the calcaneo-cuboidal joint,which can be considered to be an "adaptive joint" within a normal foot. Trauma to this region may cause fractures and/or dislocations and, in high energy trauma,compartment syndromes. Principles of treatment are immediate reduction of dislocations and realignment of the medial and lateral column of the foot in length and orientation. Open reduction and internal fixation of talus and navicular fractures are often indicated to restore the "coxa pedis". Open reconstruction or fusion in correct length of the calcaneo-cuboidal joint is occasionally indicated. Salvage procedures in malunions include navicular osteotomies and calcaneo-cuboidal bone block fusions. Treatment of joint destructions, especially involving the talo-navicular joint, include triple arthrodesis.

  17. Site specificity of DSP-PP cleavage by BMP1. (United States)

    Yang, Robert T; Lim, Glendale L; Yee, Colin T; Fuller, Robert S; Ritchie, Helena H


    Bone morphogenic protein 1 (BMP1), a metalloproteinase, is known to cleave a wide variety of extracellular matrix proteins, suggesting that a consensus substrate cleavage amino acid sequence might exist. However, while such a consensus sequence has been proposed based on P4 to P4' (i.e. the four amino acids flanking either side of the BMP1 cleavage site; P4P3P2P1|P1'P2'P3'P4') sequence homologies between two BMP1 substrates, dentin matrix protein 1 and dentin sialoprotein phosphophoryn (DSP-PP) (i.e. xMQx|DDP), no direct testing has so far been attempted. Using an Sf9 cell expression system, we have been able to produce large amounts of uncleaved DSP-PP. Point mutations introduced into this recombinant DSP-PP were then tested for their effects on DSP-PP cleavage by either Sf9 endogenous tolloid-related protein 1 (TLR-1) or by its human homolog, BMP1. Here, we have measured DSP-PP cleavage efficiencies after modifications based on P4-P4' sequence comparisons with dentin matrix protein 1, as well as for prolysyl oxidase and chordin, two other BMP1 substrates. Our results demonstrate that any mutations within or outside of the DSP-PP P4 to P4' cleavage site can block, impair or accelerate DSP-PP cleavage, and suggest that its BMP1 cleavage site is highly conserved in order to regulate its cleavage efficiency, possibly with additional assistance from its conserved exosites. Thus, BMP1 cleavage cannot be based on a consensus substrate cleavage site.

  18. Evaluations of the Irwin. beta. /sub Ic/ adjustment for small specimen fracture toughness data

    Energy Technology Data Exchange (ETDEWEB)

    Merkle, J.G.


    When small specimens are used to measure the cleavage fracture toughness of pressure vessel steels in the transition range of temperature, specimen thickness size effects and large amounts of data scatter are often observed. The size effects are manifested by an increase in the average value of fracture toughness with decreasing specimen thickness, eventually resulting in a change in fracture mode from cleavage to ductile tearing. It has been shown that a semiempirical adjustment for the interacting effects of specimen thickness, yield stress and toughness originally proposed by Irwin is capable of reducing the calculated values of toughness and data scatter to levels consistent with large specimen test data. This is true for dynamic as well as for static initiation toughness values. The nature of the size effect described by the Irwin ..beta../sub Ic/ equation is illustrated and specific cases are shown in which ..beta../sub Ic/ adjustment has eliminated size effects, for both static and dynamic fracture toughness data.

  19. Ostensible enzyme promiscuity: alkene cleavage by peroxidases. (United States)

    Mutti, Francesco G; Lara, Miguel; Kroutil, Markus; Kroutil, Wolfgang


    Enzyme promiscuity is generally accepted as the ability of an enzyme to catalyse alternate chemical reactions besides the 'natural' one. In this paper peroxidases were shown to catalyse the cleavage of a C=C double bond adjacent to an aromatic moiety for selected substrates at the expense of molecular oxygen at an acidic pH. It was clearly shown that the reaction occurs due to the presence of the enzyme; furthermore, the reactivity was clearly linked to the hemin moiety of the peroxidase. Comparison of the transformations catalysed by peroxidase and by hemin chloride revealed that these two reactions proceed equally fast; additional experiments confirmed that the peptide backbone was not obligatory for the reaction and only a single functional group of the enzyme was required, namely in this case the prosthetic group (hemin). Consequently, we propose to define such a promiscuous activity as 'ostensible enzyme promiscuity'. Thus, we call an activity that is catalysed by an enzyme 'ostensible enzyme promiscuity' if the reactivity can be tracked back to a single catalytic site, which on its own can already perform the reaction equally well in the absence of the peptide backbone.

  20. Quantification of DNA cleavage specificity in Hi-C experiments. (United States)

    Meluzzi, Dario; Arya, Gaurav


    Hi-C experiments produce large numbers of DNA sequence read pairs that are typically analyzed to deduce genomewide interactions between arbitrary loci. A key step in these experiments is the cleavage of cross-linked chromatin with a restriction endonuclease. Although this cleavage should happen specifically at the enzyme's recognition sequence, an unknown proportion of cleavage events may involve other sequences, owing to the enzyme's star activity or to random DNA breakage. A quantitative estimation of these non-specific cleavages may enable simulating realistic Hi-C read pairs for validation of downstream analyses, monitoring the reproducibility of experimental conditions and investigating biophysical properties that correlate with DNA cleavage patterns. Here we describe a computational method for analyzing Hi-C read pairs to estimate the fractions of cleavages at different possible targets. The method relies on expressing an observed local target distribution downstream of aligned reads as a linear combination of known conditional local target distributions. We validated this method using Hi-C read pairs obtained by computer simulation. Application of the method to experimental Hi-C datasets from murine cells revealed interesting similarities and differences in patterns of cleavage across the various experiments considered.

  1. Effects of crack tip geometry on dislocation emission and cleavage A possible path to enhanced ductility

    CERN Document Server

    Schiøtz, J; Carlsson, A E


    We present a systematic study of the effect of crack blunting on subsequent crack propagation and dislocation emission. We show that the stress intensity factor required to propagate the crack is increased as the crack is blunted by up to thirteen atomic layers, but only by a relatively modest amount for a crack with a sharp 60$^\\circ$ corner. The effect of the blunting is far less than would be expected from a smoothly blunted crack; the sharp corners preserve the stress concentration, reducing the effect of the blunting. However, for some material parameters blunting changes the preferred deformation mode from brittle cleavage to dislocation emission. In such materials, the absorption of preexisting dislocations by the crack tip can cause the crack tip to be locally arrested, causing a significant increase in the microscopic toughness of the crack tip. Continuum plasticity models have shown that even a moderate increase in the microscopic toughness can lead to an increase in the macroscopic fracture toughne...

  2. Effect of Natural Fractures on Hydraulic Fracturing (United States)

    Ben, Y.; Wang, Y.; Shi, G.


    Hydraulic Fracturing has been used successfully in the oil and gas industry to enhance oil and gas production in the past few decades. Recent years have seen the great development of tight gas, coal bed methane and shale gas. Natural fractures are believed to play an important role in the hydraulic fracturing of such formations. Whether natural fractures can benefit the fracture propagation and enhance final production needs to be studied. Various methods have been used to study the effect of natural fractures on hydraulic fracturing. Discontinuous Deformation Analysis (DDA) is a numerical method which belongs to the family of discrete element methods. In this paper, DDA is coupled with a fluid pipe network model to simulate the pressure response in the formation during hydraulic fracturing. The focus is to study the effect of natural fractures on hydraulic fracturing. In particular, the effect of rock joint properties, joint orientations and rock properties on fracture initiation and propagation will be analyzed. The result shows that DDA is a promising tool to study such complex behavior of rocks. Finally, the advantages of disadvantages of our current model and future research directions will be discussed.

  3. Fracture channel waves (United States)

    Nihei, Kurt T.; Yi, Weidong; Myer, Larry R.; Cook, Neville G. W.; Schoenberg, Michael


    The properties of guided waves which propagate between two parallel fractures are examined. Plane wave analysis is used to obtain a dispersion equation for the velocities of fracture channel waves. Analysis of this equation demonstrates that parallel fractures form an elastic waveguide that supports two symmetric and two antisymmetric dispersive Rayleigh channel waves, each with particle motions and velocities that are sensitive to the normal and tangential stiffnesses of the fractures. These fracture channel waves degenerate to shear waves when the fracture stiffnesses are large, to Rayleigh waves and Rayleigh-Lamb plate waves when the fracture stiffnesses are low, and to fracture interface waves when the fractures are either very closely spaced or widely separated. For intermediate fracture stiffnesses typical of fractured rock masses, fracture channel waves are dispersive and exhibit moderate to strong localization of guided wave energy between the fractures. The existence of these waves is examined using laboratory acoustic measurements on a fractured marble plate. This experiment confirms the distinct particle motion of the fundamental antisymmetric fracture channel wave (A0 mode) and demonstrates the ease with which a fracture channel wave can be generated and detected.

  4. Fractures in multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E; Jensen, K


    In a cross-sectional study of 299 MS patients 22 have had fractures and of these 17 after onset of MS. The fractures most frequently involved the femoral neck and trochanter (41%). Three patients had had more than one fracture. Only 1 patient had osteoporosis. The percentage of fractures increased...

  5. Analysis Technology of Local Fracture Behavior Based on Finite Element Method

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Yoon Suk; Lee, Sang Min; Lee, Tae Rin; Ko, Han Ok; Kim, Jong Min; Choi, Shin Beom [Sungkyunkwan Univ., Seoul (Korea, Republic of)


    The scatter of measured fracture toughness data and transferability problems among different crack configurations and loading conditions are major obstacles for application of fracture mechanics. To address these issues, recently, concerns for local approach adopting micro-mechanical damage models are being increased again in connection with a progress of computational technology. In the present research, assessment of both cleavage fracture based on Weibull statistics and ductile fracture based on GTN(Gurson-Tvergaard-Needleman) as well as Rousselier models was carried out. A series of three dimensional finite element analyses and corresponding fracture toughness tests were performed for SP(Small Punch), CT(Compact Tension) and PCVN(Pre-Cracked V-Notched) specimens. Then, failure probability analysis under three different temperatures and fracture resistance curve estimation for diverse materials have been conducted. Finally, promising results were derived through comparison between measured and predicted data. It is anticipated that the resulting cleavage fracture evaluation procedure based on the maximum likelihood method, prototype of toughness scale diagram and ductile fracture evaluation procedure using the SP specimen can be utilized to make the basis for demonstrating realistic safety margins of nuclear components containing defect.

  6. Specificity of the proteasome cleavage to the antigen protein

    Institute of Scientific and Technical Information of China (English)


    In the MHC classⅠmolecule binding antigenic peptides processing and presentation pathway,the ubiquitin-proteasome system plays a key role in degrading the protein substrate.For the purpose of studying the specificities of proteasomal cleavage sites,partial least squares method is used to predict the proteasomal cleavage sites,and the predictive accuracy of the model is 82.8%.The specificities of the cleavage sites and the adjacent positions come from the contribution of the amino acids of the samples to the cleavage sites,showing the information of proteasome interacting with antigen protein.It demonstrates that the proteasome cleaving to target protein is selective,but not random.

  7. Synthesis and Cleavage Activity of Artifical Minic Polypeptides

    Institute of Scientific and Technical Information of China (English)

    Yong YE; Xiao Lian HU; Ping LI; Ming Yu NIU; Li Feng CAO; Yu Fen ZHAO


    Two artificial minic polypeptides which are synthetic analogues of natural products with DNA affinity were synthesized, and theirs cleavage activity with DNA were examined. The structures of these compounds was confirmed by 1H NMR, MS and IR.

  8. Implementation of a combinatorial cleavage and deprotection scheme

    DEFF Research Database (Denmark)

    Nielsen, John; Rasmussen, Palle H.


    Phthalhydrazide libraries are synthesized in solution from substituted hydrazines and phthalimides in several different library formats including single compounds, indexed sub-libraries and a full library. When carried out during solid-phase synthesis, this combinatorial cleavage and deprotection...

  9. Mechanisms for ribotoxin-induced ribosomal RNA cleavage

    Energy Technology Data Exchange (ETDEWEB)

    He, Kaiyu [Department of Microbiology and Molecular Genetics (United States); Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824 (United States); Zhou, Hui-Ren [Food Science and Human Nutrition (United States); Pestka, James J., E-mail: [Department of Microbiology and Molecular Genetics (United States); Food Science and Human Nutrition (United States); Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824 (United States)


    The Type B trichothecene deoxynivalenol (DON), a ribotoxic mycotoxin known to contaminate cereal-based foods, induces ribosomal RNA (rRNA) cleavage in the macrophage via p38-directed activation of caspases. Here we employed the RAW 264.7 murine macrophage model to test the hypothesis that this rRNA cleavage pathway is similarly induced by other ribotoxins. Capillary electrophoresis confirmed that the antibiotic anisomycin (≥ 25 ng/ml), the macrocylic trichothecene satratoxin G (SG) (≥ 10 ng/ml) and ribosome-inactivating protein ricin (≥ 300 ng/ml) induced 18s and 28s rRNA fragmentation patterns identical to that observed for DON. Also, as found for DON, inhibition of p38, double-stranded RNA-activated kinase (PKR) and hematopoietic cell kinase (Hck) suppressed MAPK anisomycin-induced rRNA cleavage, while, in contrast, their inhibition did not affect SG- and ricin-induced rRNA fragmentation. The p53 inhibitor pifithrin-μ and pan caspase inhibitor Z-VAD-FMK suppressed rRNA cleavage induced by anisomycin, SG and ricin, indicating that these ribotoxins shared with DON a conserved downstream pathway. Activation of caspases 8, 9 and 3 concurrently with apoptosis further suggested that rRNA cleavage occurred in parallel with both extrinsic and intrinsic pathways of programmed cell death. When specific inhibitors of cathepsins L and B (lysosomal cysteine cathepsins active at cytosolic neutral pH) were tested, only the former impaired anisomycin-, SG-, ricin- and DON-induced rRNA cleavage. Taken together, the data suggest that (1) all four ribotoxins induced p53-dependent rRNA cleavage via activation of cathepsin L and caspase 3, and (2) activation of p53 by DON and anisomycin involved p38 whereas SG and ricin activated p53 by an alternative mechanism. Highlights: ► Deoxynivalenol (DON) anisomycin, satratoxin G (SG) and ricin are ribotoxins. ► Ribotoxins induce 18s and 28s rRNA cleavage in the RAW 264.7 macrophage model. ► Ribotoxins induce rRNA cleavage via

  10. Cleavage of a specific bond in troponin C by thrombin. (United States)

    Leavis, P C; Rosenfeld, S; Lu, R C


    Limited proteolysis of rabbit skeletal troponin C with bovine thrombin yielded two fragments, TH1 (Mr = 11000) containing Ca2+ binding regions I--III and TH2 (Mr = 6000) containing region IV. Determination of the partial sequences of the fragments established the site of cleavage at Arg120-Ala121. Secondary cleavage by thrombin at other arginyl or lysyl residues in troponin C was ruled out by the sequence data and by the amino acid compositions of the two fragments.

  11. Cell-surface acceleration of urokinase-catalyzed receptor cleavage

    DEFF Research Database (Denmark)

    Høyer-Hansen, G; Ploug, M; Behrendt, N;


    937 cell lysates, had the same amino termini as uPAR(2+3), generated by uPA in a purified system. In both cases cleavage had occurred at two positions in the hinge region connecting domain 1 and 2, between Arg83-Ala84 and Arg89-Ser90, respectively. The uPA-catalyzed cleavage of uPAR is a new negative...

  12. Improved fracture behavior and microstructural characterization of thin tungsten foils

    Directory of Open Access Journals (Sweden)

    Vladica Nikolic


    Full Text Available This study is focused towards the development of the technique for investigating the fracture behaviour of 100µm thick rolled tungsten foils, with a purity of 99.97%. Electron backscatter diffraction (EBSD scans reveal that the grains are elongated along the rolling direction of the foil, which has a very strong {100} texture. The test specimens were fabricated by electrical discharge machining (EDM and cracks were initiated by consecutively using a diamond wire saw, a razor blade and a focused ion beam (FIB workstation. Fracture experiments were performed at temperatures from −196°C to 800°C. The investigation of fracture appearance shows an improved behavior and significantly higher values of conditional fracture toughness Kq compared to bulk W-materials, which can be related to a higher degree of deformation during the production process. A high toughness at room temperature (RT and 200°C, slowly decreases when approaching the highest testing temperature of 800°C. The most significant result reveals that the ductile to brittle transition temperature (DBTT is around RT, which is an extraordinary result for any tungsten material. The fracture surfaces, investigated with a scanning electron microscope (SEM, show a transition from cleavage fracture at liquid nitrogen temperature, through pronounced delamination within the foil plane at ambient temperatures to ductile fracture at the highest testing temperatures.

  13. Cleavage events and sperm dynamics in chick intrauterine embryos.

    Directory of Open Access Journals (Sweden)

    Hyung Chul Lee

    Full Text Available This study was undertaken to elucidate detailed event of early embryogenesis in chicken embryos using a noninvasive egg retrieval technique before oviposition. White Leghorn intrauterine eggs were retrieved from 95 cyclic hens aged up to 54-56 weeks and morphogenetic observation was made under both bright field and fluorescent image in a time course manner. Differing from mammals, asymmetric cleavage to yield preblastodermal cells was observed throughout early embryogenesis. The first two divisions occurred synchronously and four polarized preblastodermal cells resulted after cruciform cleavage. Then, asynchronous cleavage continued in a radial manner and overall cell size in the initial cleavage region was smaller than that in the distal area. Numerous sperms were visible, regardless of zygotic nuclei formation. Condensed sperm heads were present mainly in the perivitelline space and cytoplasm, and rarely in the yolk region, while decondensed sperm heads were only visible in the yolk. In conclusion, apparent differences in sperm dynamics and early cleavage events compared with mammalian embryos were detected in chick embryo development, which demonstrated polarized cleavage with penetrating supernumerary sperm into multiple regions.

  14. ``Global and local approaches of fracture in the ductile to brittle regime of a low alloy steel``; ``Approches globale et locale de la rupture dans le domaine de transition fragile-ductile d`un acier faiblement allie``

    Energy Technology Data Exchange (ETDEWEB)

    Renevey, S


    The study is a contribution to the prediction of flow fracture toughness of low alloy steel and to a better knowledge of fracture behavior in the ductile to brittle transition region. Experiments were performed on a nozzle cut-off from a pressurized water reactor vessel made of steels A508C13 type steel. Axisymmetrical notched specimens were tested to study the fracture onset in a volume element while pre-cracked specimens were used to investigate cleavage fracture after stable crack growth. Systematic observations of fracture surfaces showed manganese sulfide inclusions (MnS) at cleavage sites or in the vicinity. The experimental results were used for modelling by the local approach to fracture. In a volume element the fracture is described by an original probabilistic model. This model is based on volume fraction distributions of MnS inclusions gathered in clusters and on the assumption of a competition without interaction between ductile and cleavage fracture modes. This model was applied to pre-cracked specimens (CT specimens). It is able to describe the scatter in the toughness after a small stable crack growth if a temperature effect on the cleavage stress is assumed. So, the modelling is able to give a lower bound of fracture toughness as a function of temperature. (author) 100 refs.

  15. Imaging of vertebral fractures

    Directory of Open Access Journals (Sweden)

    Ananya Panda


    Full Text Available Vertebral fracture is a common clinical problem. Osteoporosis is the leading cause of non-traumatic vertebral fracture. Often, vertebral fractures are not clinically suspected due to nonspecific presentation and are overlooked during routine interpretation of radiologic investigations. Moreover, once detected, many a times the radiologist fails to convey to the clinician in a meaningful way. Hence, vertebral fractures are a constant cause of morbidity and mortality. Presence of vertebral fracture increases the chance of fracture in another vertebra and also increases the risk of subsequent hip fracture. Early detection can lead to immediate therapeutic intervention improving further the quality of life. So, in this review, we wish to present a comprehensive overview of vertebral fracture imaging along with an algorithm of evaluation of vertebral fractures.

  16. Analysis of fracture toughness in the transition-temperature region of an Mn-Mo-Ni low-alloy steel (United States)

    Kim, Sangho; Hwang, Byoungchul; Lee, Sunghak; Lee, Sunghak


    This study is concerned with the analysis of fracture toughness in the transition region of an Mn-Mo-Ni low-alloy steel, in accordance with the ASTM E1921 standard test method. Elastic-plastic cleavage fracture toughness ( K Jc ) was determined by three-point bend tests, using precracked Charpy V-notch (PCVN) specimens, and relationships between K Jc , the critical component of J ( J c ), critical distance ( X c ), stretch-zone width (SZW), local fracture stress, and plane-strain fracture toughness ( K Ic were discussed on the basis of the cleavage fracture behavior in the transition region. The master curve and the 95 pct confidence curves well explained the variation in the measured K Jc , and the Weibull slope measured on the Weibull plots was consistent with the theoretical slope of 4. Fractographic observation indicated that X c linearly increased with increasing J c , and that the SZW had a good correlation with K Jc , irrespective of the test temperature. In addition, the local fracture stress was independent of the test temperature, because the tempered bainitic steel used in this study showed a propagation-controlled cleavage fracture behavior.

  17. Fracture Criterion for Fracture Mechanics of Magnets

    Institute of Scientific and Technical Information of China (English)

    潘灏; 杨文涛


    The applicability and limitation of some fracture criteria in the fracture mechanics of magnets are studied.It is shown that the magnetic field intensity factor can be used as a fracture criterion when the crack in a magnet is only affected by a magnetic field. For some magnetostrictive materials in which the components of magnetostriction strain do not satisfy the compatibility equation of deformation, the stress intensity factor can no longer be effectively applicable as a fracture criterion when the crack in a magnet is affected by a magnetic field and mechanical loads simultaneously.

  18. Fracture properties of neutron-irradiated martensitic 9Cr-WVTa steels below room temperature (United States)

    Abe, F.; Narui, M.; Kayano, H.


    Fracture properties of the reduced activation martensitic 9Cr-1WVTa and 9Cr-3WVTa steels were investigated by carrying out instrumented Charpy impact tests and tensile tests at temperatures below room temperature after irradiation in the Japan Materials Testing Reactor at 493 and 538 K. Modified 9Cr-1MoVNb steel was also examined for comparison. The irradiation-induced increase in ductile-to-brittle transition temperature was 53, 26 and 40 K for the {1}/{3} size Charpy specimens of 9Cr-1WVTa, 9Cr-3WVTa and 9Cr-1MoVNb steels, respectively, which resulted primarily from the irradiation-induced increase in yield stress. The cleavage fracture stress was 1820-1870 MPa for the three steels in unirradiated conditions, which was scarcely affected by irradiation. The deflections to the maximum load and to the brittle fracture initiation were decreased by irradiation. In the tensile test, quasi-cleavage fracture occurred at 77 K in both unirradiated and irradiated conditions. The cleavage fracture stress was 1320-1380 MPa for the tensile specimens of the three steels, which was about 1.4 times smaller than that for the Charpy specimens.

  19. Fracture behavior of DO3-ordered Fe-Al alloy with V addition

    Institute of Scientific and Technical Information of China (English)

    楼白杨; 鲁聪达; 金杰; 杨继隆


    The fracture behaviors of DO3-ordered Fe-28Al alloys with or without V addition were studied. The results show that addition of element V into Fe-Al alloy can improve the mechanical properties of the alloy. Contrasted with transgranular fracture of Fe3Al alloy at room temperature, the Fe3Al containing V has intergranular and transgranular cleavage mixed fracture mode. The theoretical calculation conforms that V addition could increase cleavage strength of Fe3Al alloy from 98.405 7 kJ/mol to 173.144 5 kJ/mol in 〈111〉 direction and from 29.660 4 kJ/mol to 47.673 0 kJ/mol in 〈100〉 direction.

  20. The effect of specimen and flaw dimensions on fracture toughness

    Energy Technology Data Exchange (ETDEWEB)

    Nevalainen, M.J. [VTT Manufacturing Technology, Espoo (Finland)


    The effect of the specimen size and geometry on fracture toughness has been investigated both by experimental tests and computational analyses. The methods for constraint description, namely T-stress, Q-parameter and Small-Scale Yielding Correction (SSYC) have been compared and applied for various geometries. A statistical treatment for the specimen thickness effect on cleavage fracture toughness has been investigated. Elliptical surface cracks were compared with straight-thickness cracks and a method for crack shape correction was presented. Based on the results, the differences in apparent fracture toughness values obtained from various specimen configurations can be better understood and taken into account. 64 refs. The thesis includes also four previous publications by author.

  1. Fractures in anisotropic media (United States)

    Shao, Siyi

    Rocks may be composed of layers and contain fracture sets that cause the hydraulic, mechanical and seismic properties of a rock to be anisotropic. Coexisting fractures and layers in rock give rise to competing mechanisms of anisotropy. For example: (1) at low fracture stiffness, apparent shear-wave anisotropy induced by matrix layering can be masked or enhanced by the presence of a fracture, depending on the fracture orientation with respect to layering, and (2) compressional-wave guided modes generated by parallel fractures can also mask the presence of matrix layerings for particular fracture orientations and fracture specific stiffness. This report focuses on two anisotropic sources that are widely encountered in rock engineering: fractures (mechanical discontinuity) and matrix layering (impedance discontinuity), by investigating: (1) matrix property characterization, i.e., to determine elastic constants in anisotropic solids, (2) interface wave behavior in single-fractured anisotropic media, (3) compressional wave guided modes in parallel-fractured anisotropic media (single fracture orientation) and (4) the elastic response of orthogonal fracture networks. Elastic constants of a medium are required to understand and quantify wave propagation in anisotropic media but are affected by fractures and matrix properties. Experimental observations and analytical analysis demonstrate that behaviors of both fracture interface waves and compressional-wave guided modes for fractures in anisotropic media, are affected by fracture specific stiffness (controlled by external stresses), signal frequency and relative orientation between layerings in the matrix and fractures. A fractured layered medium exhibits: (1) fracture-dominated anisotropy when the fractures are weakly coupled; (2) isotropic behavior when fractures delay waves that are usually fast in a layered medium; and (3) matrix-dominated anisotropy when the fractures are closed and no longer delay the signal. The

  2. Hip fracture surgery (United States)

    ... neck fracture repair; Trochanteric fracture repair; Hip pinning surgery; Osteoarthritis-hip ... You may receive general anesthesia before this surgery. This means ... spinal anesthesia. With this kind of anesthesia, medicine is ...

  3. Metatarsal stress fractures - aftercare (United States)

    ... page: // Metatarsal stress fractures - aftercare To use the sharing features on ... that connect your ankle to your toes. A stress fracture is a break in the bone that ...

  4. Cleavage entropy as quantitative measure of protease specificity.

    Directory of Open Access Journals (Sweden)

    Julian E Fuchs


    Full Text Available A purely information theory-guided approach to quantitatively characterize protease specificity is established. We calculate an entropy value for each protease subpocket based on sequences of cleaved substrates extracted from the MEROPS database. We compare our results with known subpocket specificity profiles for individual proteases and protease groups (e.g. serine proteases, metallo proteases and reflect them quantitatively. Summation of subpocket-wise cleavage entropy contributions yields a measure for overall protease substrate specificity. This total cleavage entropy allows ranking of different proteases with respect to their specificity, separating unspecific digestive enzymes showing high total cleavage entropy from specific proteases involved in signaling cascades. The development of a quantitative cleavage entropy score allows an unbiased comparison of subpocket-wise and overall protease specificity. Thus, it enables assessment of relative importance of physicochemical and structural descriptors in protease recognition. We present an exemplary application of cleavage entropy in tracing substrate specificity in protease evolution. This highlights the wide range of substrate promiscuity within homologue proteases and hence the heavy impact of a limited number of mutations on individual substrate specificity.

  5. Cleavage entropy as quantitative measure of protease specificity. (United States)

    Fuchs, Julian E; von Grafenstein, Susanne; Huber, Roland G; Margreiter, Michael A; Spitzer, Gudrun M; Wallnoefer, Hannes G; Liedl, Klaus R


    A purely information theory-guided approach to quantitatively characterize protease specificity is established. We calculate an entropy value for each protease subpocket based on sequences of cleaved substrates extracted from the MEROPS database. We compare our results with known subpocket specificity profiles for individual proteases and protease groups (e.g. serine proteases, metallo proteases) and reflect them quantitatively. Summation of subpocket-wise cleavage entropy contributions yields a measure for overall protease substrate specificity. This total cleavage entropy allows ranking of different proteases with respect to their specificity, separating unspecific digestive enzymes showing high total cleavage entropy from specific proteases involved in signaling cascades. The development of a quantitative cleavage entropy score allows an unbiased comparison of subpocket-wise and overall protease specificity. Thus, it enables assessment of relative importance of physicochemical and structural descriptors in protease recognition. We present an exemplary application of cleavage entropy in tracing substrate specificity in protease evolution. This highlights the wide range of substrate promiscuity within homologue proteases and hence the heavy impact of a limited number of mutations on individual substrate specificity.

  6. Identifying osteoporotic vertebral fracture


    Griffith, James F.


    Osteoporosis per se is not a harmful disease. It is the sequela of osteoporosis and most particularly the occurrence of osteoporotic fracture that makes osteoporosis a serious medical condition. All of the preventative measures, investigations, treatment and research into osteoporosis have one primary goal and that is to prevent the occurrence of osteoporotic fracture. Vertebral fracture is by far and away the most prevalent osteoporotic fracture. The significance and diagnosis of vertebral f...

  7. Imaging of insufficiency fractures

    Energy Technology Data Exchange (ETDEWEB)

    Krestan, Christian [Department of Radiology, Medical University of Vienna, Vienna General Hospital, Waehringerstr. 18-20, 1090 Vienna (Austria)], E-mail:; Hojreh, Azadeh [Department of Radiology, Medical University of Vienna, Vienna General Hospital, Waehringerstr. 18-20, 1090 Vienna (Austria)


    This review focuses on the occurrence, imaging and differential diagnosis of insufficiency fractures. Prevalence, the most common sites of insufficiency fractures and their clinical implications are discussed. Insufficiency fractures occur with normal stress exerted on weakened bone. Postmenopausal osteoporosis is the most common cause of insufficiency fractures. Other conditions which affect bone turnover include osteomalacia, hyperparathyroidism, chronic renal failure and high-dose glucocorticoid therapy. It is a challenge for the radiologist to detect and diagnose insufficiency fractures, and to differentiate them from other bone lesions. Radiographs are still the most widely used imaging method for identification of insufficiency fractures, but sensitivity is limited, depending on the location of the fractures. Magnetic resonance imaging (MRI) is a very sensitive tool to visualize bone marrow abnormalities associated with insufficiency fractures. Thin section, multi-detector computed tomography (MDCT) depicts subtle fracture lines allowing direct visualization of cortical and trabecular bone. Bone scintigraphy still plays a role in detecting fractures, with good sensitivity but limited specificity. The most important differential diagnosis is underlying malignant disease leading to pathologic fractures. Bone densitometry and clinical history may also be helpful in confirming the diagnosis of insufficiency fractures.

  8. Fracture prevention in men

    NARCIS (Netherlands)

    Geusens, PP; Sambrook, P.N.; Lems, W.F.


    The lifetime risk of experiencing a fracture in 50-year-old men is lower (20%) than the risk in women (50%). Consequently, much less research has been carried out on osteoporosis and fracture risk in men. Differences in the risk and incidence of fractures between men and women are related to differe

  9. Multi scale study of the plasticity at low temperature in {alpha}-iron: application for the cleavage; Etude multiechelle de la plasticite du fer-{alpha} a basse temperature application au clivage

    Energy Technology Data Exchange (ETDEWEB)

    Chaussidon, J


    An accident inside a nuclear power plant may lead to the cleavage of the nuclear vessel made of bainitic steel. In order to understand the origin of this fracture, we studied BCC-iron plasticity at low temperature using numerical simulations at different scales. Molecular Dynamics simulations show the high dependency of screw dislocation motion with temperature and stress. Results from these simulations were added to experiment data to develop a new Dislocation Dynamics code dedicated to BCC iron at low temperature. The code was used to model plasticity into a ferritic lath for various temperatures. This work confirms that cleavage is favoured by low temperatures. (author)

  10. A new cultural cleavage in post-modern society

    Directory of Open Access Journals (Sweden)

    Jan-Erik Lane


    Full Text Available The attitudes towards gender and homosexuality tend to be linked at the micro level (individuals, which explains the political saliency of this newly emerging cleavage. At the macro level (country, the main finding is that the value orientations towards gender and homosexuality are strongly embedded in the basic cultural or civilisation differences among countries. As developing countries modernise and enter post-modernity, they will also experience the gender cleavage, especially when they adhere to an individualistic culture. Cultural cleavages in the post-modern society, whether in rich or developing countries, can only be properly researched by the survey method. It opens up a large area for both micro and macro analyses in the social sciences.

  11. Variable context Markov chains for HIV protease cleavage site prediction. (United States)

    Oğul, Hasan


    Deciphering the knowledge of HIV protease specificity and developing computational tools for detecting its cleavage sites in protein polypeptide chain are very desirable for designing efficient and specific chemical inhibitors to prevent acquired immunodeficiency syndrome. In this study, we developed a generative model based on a generalization of variable order Markov chains (VOMC) for peptide sequences and adapted the model for prediction of their cleavability by certain proteases. The new method, called variable context Markov chains (VCMC), attempts to identify the context equivalence based on the evolutionary similarities between individual amino acids. It was applied for HIV-1 protease cleavage site prediction problem and shown to outperform existing methods in terms of prediction accuracy on a common dataset. In general, the method is a promising tool for prediction of cleavage sites of all proteases and encouraged to be used for any kind of peptide classification problem as well.

  12. New insight into the cleavage reaction of Nostoc sp. strain PCC 7120 carotenoid cleavage dioxygenase in natural and nonnatural carotenoids. (United States)

    Heo, Jinsol; Kim, Se Hyeuk; Lee, Pyung Cheon


    Carotenoid cleavage dioxygenases (CCDs) are enzymes that catalyze the oxidative cleavage of carotenoids at a specific double bond to generate apocarotenoids. In this study, we investigated the activity and substrate preferences of NSC3, a CCD of Nostoc sp. strain PCC 7120, in vivo and in vitro using natural and nonnatural carotenoid structures. NSC3 cleaved β-apo-8'-carotenal at 3 positions, C-13 C-14, C-15 C-15', and C-13' C-14', revealing a unique cleavage pattern. NSC3 cleaves the natural structure of carotenoids 4,4'-diaponeurosporene, 4,4'-diaponeurosporen-4'-al, 4,4'-diaponeurosporen-4'-oic acid, 4,4'-diapotorulene, and 4,4'-diapotorulen-4'-al to generate novel cleavage products (apo-14'-diaponeurosporenal, apo-13'-diaponeurosporenal, apo-10'-diaponeurosporenal, apo-14'-diapotorulenal, and apo-10'-diapotorulenal, respectively). The study of carotenoids with natural or nonnatural structures produced by using synthetic modules could provide information valuable for understanding the cleavage reactions or substrate preferences of other CCDs in vivo and in vitro.

  13. Microstructure evolution and fracture behaviour for electron beam welding of Ti–6Al–4V

    Indian Academy of Sciences (India)

    Wu Huiqiang; Feng Jicai; He Jingshan


    The effect of microstructural characteristics on fracture behaviour mechanism for electron beam welding of Ti–6Al–4V was investigated. The results indicated that the welded microstructure composed of coarse needle + phases presenting disordered and multidirectional short needle morphology to make fracture mechanism complex. The coarse grains in weld seam with microhardness 536 HV were easy to be fractured in the region where welding heat input was ≥ 68.8 kJ/m. There exists flat curves of Ti, Al and V, Fe concentration distribution fluctuation to cause microstructural amplitude-modulated decomposition to increase the joint ductility and cleavage strength. The uneven distribution of the partial micropores located at the interior of the specimen acting as crack initiation sites lead to non-linear branch propagating path. The + interlaced structure results in the fracture location near / interface. The existence of stacking fault structure caused pile-up of dislocation to produce micropores to be new fracture initiation sites.

  14. Micro-scale fracture experiments on zirconium hydrides and phase boundaries (United States)

    Chan, H.; Roberts, S. G.; Gong, J.


    Fracture properties of micro-scale zirconium hydrides and phase boundaries were studied using microcantilever testing methods. FIB-machined microcantilevers were milled on cross-sectional surfaces of hydrided samples, with the most highly-stressed regions within the δ-hydride film, within the α-Zr or along the Zr-hydride interface. Cantilevers were notched using the FIB and then tested in bending using a nanoindenter. Load-displacement results show that three types of cantilevers have distinct deformation properties. Zr cantilevers deformed plastically. Hydride cantilevers fractured after a small amount of plastic flow; the fracture toughness of the δ-hydride was found to be 3.3 ± 0.4 MPam1/2 and SEM examination showed transgranular cleavage on the fracture surfaces. Cantilevers notched at the Zr-hydride interface developed interfacial voids during loading, at loads considerably lower than that which initiate brittle fracture of hydrides.

  15. Stress fractures in runners. (United States)

    McCormick, Frank; Nwachukwu, Benedict U; Provencher, Matthew T


    Stress fractures are a relatively common entity in athletes, in particular, runners. Physicians and health care providers should maintain a high index of suspicion for stress fractures in runners presenting with insidious onset of focal bone tenderness associated with recent changes in training intensity or regimen. It is particularly important to recognize “high-risk” fractures, as these are associated with an increased risk of complication. A patient with confirmed radiographic evidence of a high-risk stress fracture should be evaluated by an orthopedic surgeon. Runners may benefit from orthotics, cushioned sneakers, interval training, and vitamin/calcium supplementation as a means of stress fracture prevention.

  16. Role of MRI in hip fractures, including stress fractures, occult fractures, avulsion fractures

    Energy Technology Data Exchange (ETDEWEB)

    Nachtrab, O. [Department of Radiology, The Robert Jones and Agnes Hunt Orthopaedic Hospital, Gobowen, Oswestry Shropshire SY10 7AG (United Kingdom); Cassar-Pullicino, V.N., E-mail: [Department of Radiology, The Robert Jones and Agnes Hunt Orthopaedic Hospital, Gobowen, Oswestry Shropshire SY10 7AG (United Kingdom); Lalam, R.; Tins, B.; Tyrrell, P.N.M.; Singh, J. [Department of Radiology, The Robert Jones and Agnes Hunt Orthopaedic Hospital, Gobowen, Oswestry Shropshire SY10 7AG (United Kingdom)


    MR imaging plays a vital role in the diagnosis and management of hip fractures in all age groups, in a large spectrum of patient groups spanning the elderly and sporting population. It allows a confident exclusion of fracture, differentiation of bony from soft tissue injury and an early confident detection of fractures. There is a spectrum of MR findings which in part is dictated by the type and cause of the fracture which the radiologist needs to be familiar with. Judicious but prompt utilisation of MR in patients with suspected hip fractures has a positive therapeutic impact with healthcare cost benefits as well as social care benefits.

  17. Proximal humerus fractures. (United States)

    Price, Matthew C; Horn, Pamela L; Latshaw, James C


    Proximal humerus fractures are among the most common fractures associated with osteoporosis. With an aging population, incidence of these fractures will only increase. The proximal humerus not only forms the lateral portion of the shoulder articulation but also has significant associations with musculoskeletal and neurovascular structures. As a result, fractures of the proximal humerus can significantly impact not only the function of the shoulder joint, but the health and function of the entire upper extremity as well. Understanding of these fractures, the management options, and associated nursing care, can help reduce morbidity rate and improve functional outcomes.

  18. Prediction of proteasome cleavage motifs by neural networks

    DEFF Research Database (Denmark)

    Kesimir, C.; Nussbaum, A.K.; Schild, H.


    physiological conditions. Our algorithm has been trained not only on in vitro data, but also on MHC Class I ligand data, which reflect a combination of immunoproteasome and constitutive proteasome specificity. This feature, together with the use of neural networks, a non-linear classification technique, make...... the prediction of MHC Class I ligand boundaries more accurate: 65% of the cleavage sites and 85% of the non-cleavage sites are correctly determined. Moreover, we show that the neural networks trained on the constitutive proteasome data learns a specificity that differs from that of the networks trained on MHC...

  19. Orbital fractures: a review

    Directory of Open Access Journals (Sweden)

    Jeffrey M Joseph


    Full Text Available Jeffrey M Joseph, Ioannis P GlavasDivision of Ophthalmic Plastic and Reconstructive Surgery, Department of Ophthalmology, School of Medicine, New York University, New York, NY, USA; Manhattan Eye, Ear, and Throat Hospital, New York, NY, USAAbstract: This review of orbital fractures has three goals: 1 to understand the clinically relevant orbital anatomy with regard to periorbital trauma and orbital fractures, 2 to explain how to assess and examine a patient after periorbital trauma, and 3 to understand the medical and surgical management of orbital fractures. The article aims to summarize the evaluation and management of commonly encountered orbital fractures from the ophthalmologic perspective and to provide an overview for all practicing ophthalmologists and ophthalmologists in training.Keywords: orbit, trauma, fracture, orbital floor, medial wall, zygomatic, zygomatic complex, zmc fracture, zygomaticomaxillary complex fractures 

  20. [Fractures of carpal bones]. (United States)

    Lögters, T; Windolf, J


    Fractures of the carpal bones are uncommon. On standard radiographs fractures are often not recognized and a computed tomography (CT) scan is the diagnostic method of choice. The aim of treatment is to restore pain-free and full functioning of the hand. A distinction is made between stable and unstable carpal fractures. Stable non-displaced fractures can be treated conservatively. Unstable and displaced fractures have an increased risk of arthritis and non-union and should be stabilized by screws or k‑wires. If treated adequately, fractures of the carpal bones have a good prognosis. Unstable and dislocated fractures have an increased risk for non-union. The subsequent development of carpal collapse with arthrosis is a severe consequence of non-union, which has a heterogeneous prognosis.

  1. Atomistic study of hydrogen embrittlement of grain boundaries in nickel: I. Fracture (United States)

    Tehranchi, A.; Curtin, W. A.

    Hydrogen ingress into a metal is a persistent source of embrittlement. Fracture surfaces are often intergranular, suggesting favorable cleave crack growth along grain boundaries (GBs) as one driver for embrittlement. Here, atomistic simulations are used to investigate the effects of segregated hydrogen on the behavior of cracks along various symmetric tilt grain boundaries in fcc Nickel. An atomistic potential for Ni-H is first recalibrated against new quantum level computations of the energy of H in specific sites within the NiΣ5(120)⟨100⟩ GB. The binding energy of H atoms to various atomic sites in the NiΣ3(111) (twin), NiΣ5(120)⟨100⟩, NiΣ99(557)⟨110⟩, and NiΣ9(221)⟨110⟩ GBs, and to various surfaces created by separating these GBs into two possible fracture surfaces, are computed and used to determine equilibrium H concentrations at bulk H concentrations typical of embrittlement in Ni. Mode I fracture behavior is then studied, examining the influence of H in altering the competition between dislocation emission (crack blunting; "ductile" behavior) and cleavage fracture ("brittle" behavior) for intergranular cracks. Simulation results are compared with theoretical predictions (Griffith theory for cleavage; Rice theory for emission) using the computed surface energies. The deformation behavior at the GBs is, however, generally complex and not as simple as cleavage or emission at a sharp crack tip, which is not unexpected due to the complexity of the GB structures. In cases predicted to emit dislocations from the crack tip, the presence of H atoms reduces the critical load for emission of the dislocations and no cleavage is found. In the cases predicted to cleave, the presence of H atoms reduces the cleavage stress intensity and makes cleavage easier, including NiΣ9(221)⟨110⟩ which emits dislocations in the absence of H. Aside from the one unusual NiΣ9(221)⟨110⟩ case, no tendency is found for H to cause a ductile

  2. [Fracture endoprosthesis of distal humerus fractures]. (United States)

    Müller, L P; Wegmann, K; Burkhart, K J


    The treatment of choice for fractures of the distal humerus is double plate osteosynthesis. Due to anatomical preshaped angle stable plates the primary stability and management of soft tissues has been improved. However, osteoporotic comminuted fractures in the elderly are often not amenable to stable osteosynthesis and total elbow arthroplasty has been established as an alternative therapy. Although complication rates have been reduced, complications of total elbow arthroplasty are still much more frequent than in total hip replacement. Furthermore, patients are advised not to exceed a weight bearing of 5 kg. Therefore, the indications for elbow arthroplasty must be evaluated very strictly and should be reserved for comminuted distal humeral fractures in the elderly with poor bone quality that are not amenable to stable osteosynthesis or for simple fractures in cases of preexisting symptomatic osteoarthritis. This article introduces and discusses modern concepts of elbow arthroplasty, such as modular convertible prosthesis systems, hemiarthroplasty and radial head replacement in total elbow arthroplasty.

  3. Kinetics of phycocyanobilin cleavage from C-phycocyanin by methanolysis

    DEFF Research Database (Denmark)

    Malwade, Chandrakant Ramkrishna; Roda Serrat, Maria Cinta; Christensen, Knud Villy


    Phycocyanobilin (PCB) is an important linear tetrapyrrolic molecule for food as well as pharmaceutical industry. It is obtained from blue-green algae, where it is attached covalently to phycobiliproteins (C-PC and APC) present in the light harvesting complexes. In this work, cleavage of PCB from...

  4. Mitochondria localize to the cleavage furrow in mammalian cytokinesis. (United States)

    Lawrence, Elizabeth J; Mandato, Craig A


    Mitochondria are dynamic organelles with multiple cellular functions, including ATP production, calcium buffering, and lipid biosynthesis. Several studies have shown that mitochondrial positioning is regulated by the cytoskeleton during cell division in several eukaryotic systems. However, the distribution of mitochondria during mammalian cytokinesis and whether the distribution is regulated by the cytoskeleton has not been examined. Using live spinning disk confocal microscopy and quantitative analysis of mitochondrial fluorescence intensity, we demonstrate that mitochondria are recruited to the cleavage furrow during cytokinesis in HeLa cells. After anaphase onset, the mitochondria are recruited towards the site of cleavage furrow formation, where they remain enriched as the furrow ingresses and until cytokinesis completion. Furthermore, we show that recruitment of mitochondria to the furrow occurs in multiple mammalian cells lines as well as in monopolar, bipolar, and multipolar divisions, suggesting that the mechanism of recruitment is conserved and robust. Using inhibitors of cytoskeleton dynamics, we show that the microtubule cytoskeleton, but not actin, is required to transport mitochondria to the cleavage furrow. Thus, mitochondria are specifically recruited to the cleavage furrow in a microtubule-dependent manner during mammalian cytokinesis. Two possible reasons for this could be to localize mitochondrial function to the furrow to facilitate cytokinesis and / or ensure accurate mitochondrial inheritance.

  5. Comparative study of fracture appearance in crack tip opening angle testing of gas pipeline steels

    Energy Technology Data Exchange (ETDEWEB)

    Hashemi, S.H., E-mail: [Department of Mechanical Engineering, The University of Birjand, PO Box 97175-376, Birjand (Iran, Islamic Republic of)


    The crack tip opening angle (CTOA) experiments were conducted on API X65, X70, X80 and X100 steels using a modified double cantilever beam (MDCB) geometry. The fracture surfaces of the test specimens were examined after fracture tests by optical and scanning electron microscopy. The fracture surfaces of the lower grade X65 and X70 steels had fully ductile features including classic flat and slant fracture characteristics. However, repetitive propagation and arrest of quasi-cleavage in the form of chevron arrow-head fractures was observed on the fracture surfaces of higher grade X80 and X100 steels. Interestingly, the analysis of load-displacement records from the latter steels demonstrated local ragged patterns after the test peak load, associated with the repetitive low energy quasi-cleavage mechanism. Detailed discussion on the micro-fractographs of the tested steels and comparison of the test observations with the only newly published work in this filed conclude the paper.

  6. Jaw fractures in children. (United States)

    Kotilainen, R; Kärjä, J; Kullaa-Mikkonen, A


    From a total of 350 jaw fractures treated in 1980-1984 at Kuopio University Central Hospital, 20% were in children. These injuries were evaluated retrospectively regarding age, sex, incidence and etiology. Forty-five of the patients were boys and 25 girls. The frequency of maxillary and mandibular fractures in 70 young patients was 28.6%. The most common type of bone fractures was fracture of the alveolar process, which was prevalent in persons with mixed dentition. Before the age of 7 years, falls from height were the common causes of jaw fractures. The major cause of the jaw fractures in children from 7 to 15 years old was road accidents (47.1%), especially in boys. Most of these were cycling accidents, only a few patients were victims of automobile accidents. In addition, about one third (25.7%) of the patients were treated in the hospital because of multiple injuries to other organs.

  7. Pelvic fractures and mortality.


    K.H. Chong; DeCoster, T.; Osler, T.; Robinson, B.


    A retrospective study of all patients (N = 343) with pelvic fractures admitted to our trauma service was conducted to evaluate the impact of pelvic fractures on mortality. All patients sustained additional injuries with an average Injury Severity Score (ISS) of twenty. Thirty-six patients died. This group had more severe pelvic fractures as graded by the Tile classification as well as a greater number and severity of associated injuries. Six patients died as a direct result of pelvic hemorrha...

  8. Oblique Axis Body Fracture

    DEFF Research Database (Denmark)

    Takai, Hirokazu; Konstantinidis, Lukas; Schmal, Hagen;


    was uneventful. Conclusions. Oblique type axis body fractures resemble a highly unstable subtype of Anderson type III fractures with the potential of severe secondary deformity following conservative treatment, irrespective of initial grade of displacement. The authors therefore warrant a high index of suspicion......Purpose. Anderson type III odontoid fractures have traditionally been considered stable and treated conservatively. However, unstable cases with unfavorable results following conservative treatment have been reported. Methods. We present the cases of two patients who sustained minimally displaced...

  9. [(Impending) pathological fracture]. (United States)

    Sutter, P M; Regazzoni, P


    Pathological fractures will be encountered in increasing frequency due to more patients with cancer, surviving a longer period. The skeleton is the third most frequent localization for metastases. Breast cancer is still the most common primary tumor, but bone metastases from lung cancer seem to be diagnosed more and more. Despite of finding metastases most often in the spinal column, fractures are seen mostly at the femoral site. A pathological fracture and, in almost all cases, an impending fracture are absolute indication for operation. An exact definition of an "impending fracture" is still lacking; it is widely accepted, that 50 per cent of bone mass must be destroyed before visualization in X-ray is possible, thus defining an impending fracture. The score system by Mirels estimates the fracture risk by means of four parameters (localization, per cent of destructed bone mass, type of metastasis, pain). Improving quality of life, relieving pain, preferably with a single operation and a short length of stay are the goals of (operative) treatment. For fractures of the proximal femur, prosthetic replacement, for fractures of the subtrochanteric region or the shaft, intramedullary nails are recommended. Postoperative radiation therapy possibly avoids tumor progression. In patient with a good long term prognosis, tumor should be removed locally aggressive.

  10. Scaphoid fractures in children

    Directory of Open Access Journals (Sweden)

    Gajdobranski Đorđe


    Full Text Available Introduction. Scaphoid fractures are rare in childhood. Diagnosis is very difficult to establish because carpal bones are not fully ossified. In suspected cases comparative or delayed radiography is used, as well as computerized tomography, magnetic resonance imaging, ultrasound and bone scintigraphy. Majority of scaphoid fractures are treated conservatively with good results. In case of delayed fracture healing various types of treatment are available. Objective. To determine the mechanism of injury, clinical healing process, types and outcome of treatment of scaphoid fractures in children. Methods. We retrospectively analyzed patients with traumatic closed fracture of the scaphoid bone over a ten-year period (2002-2011. The outcome of the treatment of “acute” scaphoid fracture was evaluated using the Mayo Wrist Score. Results. There were in total 34 patients, of mean age 13.8 years, with traumatic closed fracture of the scaphoid bone, whose bone growth was not finished yet. Most common injury mechanism was fall on outstretched arm - 76% of patients. During the examined period 31 children with “acute” fracture underwent conservative treatment, with average immobilization period of 51 days. Six patients were lost to follow-up. In the remaining 25 patients, after completed rehabilitation, functional results determined by the Mayo Wrist Score were excellent. Conclusion. Conservative therapy of “acute” scaphoid fractures is an acceptable treatment option for pediatric patients with excellent functional results.

  11. Atraumatic First Rib Fracture

    Directory of Open Access Journals (Sweden)

    Koray Aydogdu


    Full Text Available Rib fractures are usually seen after a trauma, while atraumatic spontaneous rib fractures are quite rare. A first rib fracture identified in our 17 years old female patient who had not a history of trauma except lifting a heavy weight was examined in details in terms of the potential complications and followed-up for a long time. We presented our experience on this case with atraumatic first rib fracture that has different views for the etiology in light of the literature.

  12. An Examination Of Fracture Splitting Parameters Of Crackable Connecting Rods

    Directory of Open Access Journals (Sweden)

    Zafer Özdemir


    Full Text Available Fracture splitting method is an innovative processing technique in the field of automobile engine connecting rod (con/rod manufacturing. Compared with traditional method, this technique has remarkable advantages. Manufacturing procedures, equipment and tools investment can be decreased and energy consumption reduced remarkably. Furthermore, product quality and bearing capability can also be improved. It provides a high quality, high accuracy and low cost route for producing connecting rods (con/rods. With the many advantages mentioned above, this method has attracted manufacturers attention and has been utilized in many types of con/rod manufacturing. In this article, the method and the advantages it provides, such as materials, notches for fracture splitting, fracture splitting conditions and fracture splitting equipment are discussed in detail. The paper describes an analysis of examination of fracture splitting parameters and optik-SEM fractography of C70S6 crackable connectıng rod. Force and velocity parameters are investigated. That uniform impact force distrubition starting from the starting notch causes brittle and cleavage failure mode is obtained as a result. This induces to decrease the toughness.

  13. Fracture of the styloid process associated with the mandible fracture

    Directory of Open Access Journals (Sweden)

    K N Dubey


    Full Text Available Fracture of the styloid process (SP of temporal bone is an uncommon injuries. Fracture of the SP can be associated with the facial injuries including mandible fracture. However, injury to the SP may be concealed and missed diagnosis may lead to the improper or various unnecessary treatments. A rare case of SP fracture associated with the ipsilateral mandibular fracture and also the diagnostic and management considerations of the SP fracture are discussed.

  14. Crossing grain boundaries in metals by slip bands, cleavage and fatigue cracks. (United States)

    Pineau, André


    The size and the character (low and large angle, special boundaries, tilt and twist boundaries, twins) of the grain boundaries (GBs) in polycrystalline materials influence their strength and their fracture toughness. Recent studies devoted to nanocrystalline (NC) materials have shown a deviation from the Hall-Petch law. Special GBs formed by Σ3 twins in face-centred cubic metals are also known to have a strong effect on the mechanical behaviour of these metals, in particular their work-hardening rate. Grain orientation influences also crack path, the fracture toughness of body-centred cubic (BCC) metals and the fatigue crack growth rate of microstructurally short cracks. This paper deals both with slip transfer at GBs and with the interactions between propagating cracks with GBs. In the analysis of slip transfer, the emphasis is placed on twin boundaries (TBs) for which the dislocation reactions during slip transfer are analysed theoretically, experimentally and using the results of atomic molecular simulations published in the literature. It is shown that in a number of situations this transfer leads to a normal motion of the TB owing to the displacement of partial dislocations along the TB. This motion can generate a de-twinning effect observed in particular in NC metals. Crack propagation across GBs is also considered. It is shown that cleavage crack path behaviour in BCC metals is largely dependent on the twist component of the GBs. A mechanism for the propagation of these twisted cracks involving a segmentation of the crack front and the existence of intergranular parts is discussed and verified for a pressure vessel steel. A similar segmentation seems to occur for short fatigue cracks although, quite surprisingly, this crossing mechanism for fatigue cracks does not seem to have been examined in very much detail in the literature. Metallurgical methods used to improve the strength of the materials, via grain boundaries, are briefly discussed.

  15. Pneumothorax complicating isolated clavicle fracture. (United States)

    Hani, Redouane; Ennaciri, Badr; Jeddi, Idriss; El Bardouni, Ahmed; Mahfoud, Mustapha; Berrada, Mohamed Saleh


    Isolated clavicle fractures are among the commonest of traumatic fractures in the emergency department. Complications of isolated clavicle fractures are rare. Pneumothorax has been described as a complication of a fractured clavicle only rarely in English literature. In all the reported cases, the pneumothorax was treated by a thoracostomy and the clavicle fracture was treated conservatively. In our case, the pneumothorax required a chest drain insertion and the clavicle fracture was treated surgically with good result.

  16. Development and application of bond cleavage reactions in bioorthogonal chemistry. (United States)

    Li, Jie; Chen, Peng R


    Bioorthogonal chemical reactions are a thriving area of chemical research in recent years as an unprecedented technique to dissect native biological processes through chemistry-enabled strategies. However, current concepts of bioorthogonal chemistry have largely centered on 'bond formation' reactions between two mutually reactive bioorthogonal handles. Recently, in a reverse strategy, a collection of 'bond cleavage' reactions has emerged with excellent biocompatibility. These reactions have expanded our bioorthogonal chemistry repertoire, enabling an array of exciting new biological applications that range from the chemically controlled spatial and temporal activation of intracellular proteins and small-molecule drugs to the direct manipulation of intact cells under physiological conditions. Here we highlight the development and applications of these bioorthogonal cleavage reactions. Furthermore, we lay out challenges and propose future directions along this appealing avenue of research.

  17. 4-Dimethylaminoazobenzenes: carcinogenicities and reductive cleavage by microsomal azo reductase. (United States)

    Lambooy, J P; Koffman, B M


    Twenty-four 4-dimethylaminoazobenzenes (DABs) in which systematic structural modifications have been made in the prime ring have been studied for substrate specificity for microsomal azo reductase. The DABs were also evaluated for carcinogenicity and it was found that there was no correlation between carcinogenicity and extent of azo bond cleavage by azo reductase. While any substituent in the prime ring reduces the rate of cleavage of the azo bond relative to the unsubstituted dye, there is a correlation between substituent size and susceptibility to the enzyme. Substituent size was also found to be a significant factor in the induction of hepatomas by the dyes. Preliminary studies have shown that there appears to be a positive correlation between microsomal riboflavin content and the activity of the azo reductase.

  18. Sequence specific inhibition of DNA restriction enzyme cleavage by PNA

    DEFF Research Database (Denmark)

    Nielsen, P.E.; Egholm, M.; Berg, R.H.


    Plasmids containing double-stranded 10-mer PNA (peptide nucleic acid chimera) targets proximally flanked by two restriction enzyme sites were challenged with the complementary PNA or PNAs having one or two mismatches, and the effect on the restriction enzyme cleavage of the flanking sites...... was assayed. The following PNAs were used: T10-LysNH2, T5CT4-LysNH2 and T2CT2CT4-LysNH2 and the corresponding targets cloned into pUC 19 were flanked by BamH1, Sal1 or Pstl sites, respectively. In all cases it was found that complete inhibition of restriction enzyme cleavage was obtained...

  19. Glutamic Acid Selective Chemical Cleavage of Peptide Bonds. (United States)

    Nalbone, Joseph M; Lahankar, Neelam; Buissereth, Lyssa; Raj, Monika


    Site-specific hydrolysis of peptide bonds at glutamic acid under neutral aqueous conditions is reported. The method relies on the activation of the backbone amide chain at glutamic acid by the formation of a pyroglutamyl (pGlu) imide moiety. This activation increases the susceptibility of a peptide bond toward hydrolysis. The method is highly specific and demonstrates broad substrate scope including cleavage of various bioactive peptides with unnatural amino acid residues, which are unsuitable substrates for enzymatic hydrolysis.

  20. Cleavage Mapping the Topology of Protein Folding Intermediates (United States)


    investigate the changes that occur in two of these mutants. V66L has a greatly lowered m value while that of A90S is substantially increased (5...stability of the folded state of nuclease. The cleavage technique will be used to investigate the changes that occur in two of these mutants. V66L...Connecticut, 06520 3Instituto de Qufmica y Fisicoquimica Biolögicas, Facultad de Farmacia y Bioqufmica (UBA-CONICET), Buenos Aires, Argentina 4

  1. Recent cleavages in the religious right in Turkey



    Ankara : Department of Political Science and Public Administration, Bilkent Univ., 1993. Thesis (Master's) -- Bilkent University, 1993. Includes bibliographical references. In this study,recent cleavages within the Prosperity Party is described. For this purpose, first the ideologies of the National Order Party and the National Salvation Party are taken up. For the PP is the continuation of the NOP and NSP, the PP cannot be understood as distinct from these two parties...

  2. Relationship between synthesis and cleavage of poliovirus-specific proteins.


    Thomas, A.A.; Voorma, H O; Boeye, A.


    Poliovirus proteinase was studied in vitro in lysates from poliovirus-infected HeLa cells. Preincubation of these lysates caused (i) a reduction in poliovirus proteinase activity and (ii) a partial dependence on exogenous mRNA for optimal translation. Proteins translated from endogenous poliovirus RNA in preincubated extracts from virus-infected HeLa cells are poorly cleaved. This cleavage deficiency is alleviated by adding fresh poliovirus RNA to the translation system, thus, allowing re-ini...

  3. Effects of Cysteamine on Sheep Embryo Cleavage Rates

    Directory of Open Access Journals (Sweden)

    Sinem Ö. ENGİNLER


    Full Text Available Oxidative stress during in vitro culture leads to defects in development of gametes and embryos. Several antioxidants such as cysteamine, L-ascorbic acid, beta mercaptoethanol, cysteine, glutathione, proteins, vitamins have been used to supplement culture media to counter the oxidative stress. This study was conducted to detect the effect of adding cysteamine to the maturation medium to subsequent cleavage rates of sheep embryos. Totally 604 ovaries were obtained by ten replica and 2060 oocytes were collected. The cumulus oocyte complexes were recovered by the slicing method. A total of 1818 selected oocytes were divided into two groups and used for maturation (88.25%. The first group was created as supplemented with cysteamine (Group A and second group (Group B, control without cysteamine in TCM-199. The two groups were incubated for 24 h at 38.8 °C in an atmosphere of 5% CO2 in humidified air for in vitro maturation (IVM. After IVM, oocytes were fertilized with 50 x 107 / mL fresh ram semen in BSOF medium for 18 h. After fertilization, maturation groups were divided into two subgroups with different culture media: Group AI-SOF (Synthetic Oviduct Fluid medium, Group AII-CR1aa (Charles Rosencrans medium, Group BI-SOF and Group BII-CR1aa were achieved. Cleavage rates were evaluated at day 2. post insemination. The rates of cleavage were detected as 59.54% (184/309, 55.44% (173/312, 65.34% (215/329, 59.34% (200/337 respectively, with showing no statistically significant difference between the groups at the level of P>0.05. In conclusion, supplementing cysteamine to maturation media in TCM-199 did not affect the cleavage rates of sheep embryos in SOF and CR1aa culture media.

  4. Deformation-dependent enzyme mechanokinetic cleavage of type I collagen. (United States)

    Wyatt, Karla E-K; Bourne, Jonathan W; Torzilli, Peter A


    Collagen is a key structural protein in the extracellular matrix of many tissues. It provides biological tissues with tensile mechanical strength and is enzymatically cleaved by a class of matrix metalloproteinases known as collagenases. Collagen enzymatic kinetics has been well characterized in solubilized, gel, and reconstituted forms. However, limited information exists on enzyme degradation of structurally intact collagen fibers and, more importantly, on the effect of mechanical deformation on collagen cleavage. We studied the degradation of native rat tail tendon fibers by collagenase after the fibers were mechanically elongated to strains of epsilon=1-10%. After the fibers were elongated and the stress was allowed to relax, the fiber was immersed in Clostridium histolyticum collagenase and the decrease in stress (sigma) was monitored as a means of calculating the rate of enzyme cleavage of the fiber. An enzyme mechanokinetic (EMK) relaxation function T(E)(epsilon) in s(-1) was calculated from the linear stress-time response during fiber cleavage, where T(E)(epsilon) corresponds to the zero order Michaelis-Menten enzyme-substrate kinetic response. The EMK relaxation function T(E)(epsilon) was found to decrease with applied strain at a rate of approximately 9% per percent strain, with complete inhibition of collagen cleavage predicted to occur at a strain of approximately 11%. However, comparison of the EMK response (T(E) versus epsilon) to collagen's stress-strain response (sigma versus epsilon) suggested the possibility of three different EMK responses: (1) constant T(E)(epsilon) within the toe region (epsiloncollagen triple helix may be by a conformational change in the triple helix since the decrease in T(E)(epsilon) appeared concomitant with stretching of the collagen molecule.

  5. Radial head fracture - aftercare (United States)

    ... Philadelphia, PA: Elsevier Saunders; 2015:chap 6. Prawer A. Radius and ulna fractures. In: Eiff M, Hatch R, eds. Fracture Management for Primary Care . 3rd ed. Philadelphia, PA: Elsevier Saunders; 2012:chap ... PhD, and the A.D.A.M. Editorial team. Related MedlinePlus Health ...


    Institute of Scientific and Technical Information of China (English)



    Objective. To investigate the unique characteristics and treatment of thoracic spine fractures.Methods. Severty-seven patients with thoracic spine fractures were retrospectively reviewed. Of these, therewere 37 compressior fractures, 34 fracture-dislocations, 3 burst fractures and 3 burst-dislocations. Twenty-six pa-tients had a complete lesion of the spinal cord, 14 sustained a neurologically incomplete injury, and 37 wereneurologically intact. Fifty-three patients were treated nonoperatively and 24 treated operatively.Results. All patients were followed up for 2 ~ 15 years. None of the 26 patients with a complete lesion recov-ered any significant function. Of 37 neurologically intact patients, 13 had local pain although all of them re-mained normal function. Two of 14 patients with incomplete paraplegia returned to normal, 7 recovered some func-tion and 5 did not recovered.Conclusions. E ecause of the unique anatomy and biomechanics of the thoracic spine, the classification common-ly applied to thoracolumbar fractures is not suitable for thoracic fractures. Fusion and instrumentation are indicat-ed when the fractures are unstable, while patients with incomplete lesion of the spinal cord may be the candidatesfor supplemented decompression.

  7. Vertebral Fracture Prediction

    DEFF Research Database (Denmark)


    Vertebral Fracture Prediction A method of processing data derived from an image of at least part of a spine is provided for estimating the risk of a future fracture in vertebraeof the spine. Position data relating to at least four neighbouring vertebrae of the spine is processed. The curvature...

  8. Hyperphosphorylation and cleavage at D421 enhance tau secretion.

    Directory of Open Access Journals (Sweden)

    Vanessa Plouffe

    Full Text Available It is well established that tau pathology propagates in a predictable manner in Alzheimer's disease (AD. Moreover, tau accumulates in the cerebrospinal fluid (CSF of AD's patients. The mechanisms underlying the propagation of tau pathology and its accumulation in the CSF remain to be elucidated. Recent studies have reported that human tau was secreted by neurons and non-neuronal cells when it was overexpressed indicating that tau secretion could contribute to the spreading of tau pathology in the brain and could lead to its accumulation in the CSF. In the present study, we showed that the overexpression of human tau resulted in its secretion by Hela cells. The main form of tau secreted by these cells was cleaved at the C-terminal. Surprisingly, secreted tau was dephosphorylated at several sites in comparison to intracellular tau which presented a strong immunoreactivity to all phospho-dependent antibodies tested. Our data also revealed that phosphorylation and cleavage of tau favored its secretion by Hela cells. Indeed, the mimicking of phosphorylation at 12 sites known to be phosphorylated in AD enhanced tau secretion. A mutant form of tau truncated at D421, the preferential cleavage site of caspase-3, was also significantly more secreted than wild-type tau. Taken together, our results indicate that hyperphosphorylation and cleavage of tau by favoring its secretion could contribute to the propagation of tau pathology in the brain and its accumulation in the CSF.

  9. Failure of cell cleavage induces senescence in tetraploid primary cells. (United States)

    Panopoulos, Andreas; Pacios-Bras, Cristina; Choi, Justin; Yenjerla, Mythili; Sussman, Mark A; Fotedar, Rati; Margolis, Robert L


    Tetraploidy can arise from various mitotic or cleavage defects in mammalian cells, and inheritance of multiple centrosomes induces aneuploidy when tetraploid cells continue to cycle. Arrest of the tetraploid cell cycle is therefore potentially a critical cellular control. We report here that primary rat embryo fibroblasts (REF52) and human foreskin fibroblasts become senescent in tetraploid G1 after drug- or small interfering RNA (siRNA)-induced failure of cell cleavage. In contrast, T-antigen-transformed REF52 and p53+/+ HCT116 tumor cells rapidly become aneuploid by continuing to cycle after cleavage failure. Tetraploid primary cells quickly become quiescent, as determined by loss of the Ki-67 proliferation marker and of the fluorescent ubiquitination-based cell cycle indicator/late cell cycle marker geminin. Arrest is not due to DNA damage, as the γ-H2AX DNA damage marker remains at control levels after tetraploidy induction. Arrested tetraploid cells finally become senescent, as determined by SA-β-galactosidase activity. Tetraploid arrest is dependent on p16INK4a expression, as siRNA suppression of p16INK4a bypasses tetraploid arrest, permitting primary cells to become aneuploid. We conclude that tetraploid primary cells can become senescent without DNA damage and that induction of senescence is critical to tetraploidy arrest.

  10. Examination of Early Cleavage an its Importance in IVF Treatment

    Directory of Open Access Journals (Sweden)

    Fancsovits P


    Full Text Available Since the introduction of assisted reproduction, the number of multiple pregnancies has increased due to the high number of transferred embryos. There is an urgent need for IVF specialists to reduce the number of embryos transferred without the risk of decreasing pregnancy rates. Embryos are selected for transfer on the basis of their developmental stage and morphology. The number of blastomeres of the embryo indicates the speed of early embryo development which correlates to the viability of the embryo. Examination of early embryo development, especially the timing of the first cleavage, can be recommended as a tool for predicting embryo viability. Observation of timing of the first cleavage and its different stages helps us to identify fast- and slow-developing embryos. Early pronuclear breakdown and early cleavage of the zygote are indicators of fast embryo development and good embryo viability. Thereby, they can lead to high implantation and pregnancy rates. The aim of this paper is to provide an overview of the timing of early embryo development and to show its significance in IVF treatment.

  11. The influence of hydride on fracture toughness of recrystallized Zircaloy-4 cladding

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Hsiao-Hung, E-mail: [Institute of Nuclear Energy Research (INER), Lungtan Township, Taoyuan County 32546, Taiwan, ROC (China); China Steel Corporation, Hsiao Kang District, Kaohsiung 81233, Taiwan, ROC (China); Chiang, Ming-Feng [China Steel Corporation, Hsiao Kang District, Kaohsiung 81233, Taiwan, ROC (China); Chen, Yen-Chen [Institute of Nuclear Energy Research (INER), Lungtan Township, Taoyuan County 32546, Taiwan, ROC (China)


    In this work, RXA cladding tubes were hydrogen-charged to target hydrogen content levels between 150 and 800 wppm (part per million by weight). The strings of zirconium hydrides observed in the cross sections are mostly oriented in the circumferential direction. The fracture toughness of hydrided RXA Zircaloy-4 cladding was measured to evaluate its hydride embrittlement susceptibility. With increasing hydrogen content, the fracture toughness of hydrided RXA cladding decreases at both 25 °C and 300 °C. Moreover, highly localized hydrides (forming a hydride rim) aggravate the degradation of the fracture properties of RXA Zircaloy-4 cladding at both 25 °C and 300 °C. Brittle features in the form of quasi-cleavages and secondary cracks were observed on the fracture surface of the hydride rim, even for RXA cladding tested at 300 °C.

  12. Bending Properties and Fracture Behavior of Ti-23Al-17Nb Alloy Laser Beam Welding Joints

    Institute of Scientific and Technical Information of China (English)

    WANG Guoqing; WU Aiping; ZOU Guisheng; ZHAO Yue; CHEN Qiang; REN Jialie


    Ti-23Al-17Nb alloy is an important high temperature structural material used in the space and aerospace fields. Welding of this alloy is an indispensable processing method, so the microstructures and mechanical properties of these welded joints must be studied to improve the welds. Longitudinal three-point bending tests were conducted to measure the bending ductility of laser beam welded joints. The crack dis-tribution and fracture surface were investigated to further analyze the fracture behavior. The results indicate that the bending ductility decreases as the heat input by the laser beam welding increases. The crack in-ducing strain reaches 4.24%, while the fracturing strain exceeds 5% when the heat input is below 316 J/cm. If the columnar crystal grain of the weld metal exhibits a uniform orientation, the bending ductility is worse. The fractography analysis shows that the cracking propagates transgranularly and the fracture surface has a cleavage mode.

  13. Dynamic fracture mechanics (United States)

    Kobayashi, A. S.; Ramulu, M.


    Dynamic fracture and crack propagation concepts for ductile materials are reviewed. The equations for calculating dynamic stress integrity and the dynamic energy release rate in order to study dynamic crack propagation are provided. The stress intensity factor versus crack velocity relation is investigated. The uses of optical experimental techniques and finite element methods for fracture analyses are described. The fracture criteria for a rapidly propagating crack under mixed mode conditions are discussed; crack extension and fracture criteria under combined tension and shear loading are based on maximum circumferential stress or energy criteria such as strain energy density. The development and use of a Dugdale model and finite element models to represent crack and fracture dynamics are examined.

  14. Transphyseal Distal Humerus Fracture. (United States)

    Abzug, Joshua; Ho, Christine Ann; Ritzman, Todd F; Brighton, Brian


    Transphyseal distal humerus fractures typically occur in children younger than 3 years secondary to birth trauma, nonaccidental trauma, or a fall from a small height. Prompt and accurate diagnosis of a transphyseal distal humerus fracture is crucial for a successful outcome. Recognizing that the forearm is not aligned with the humerus on plain radiographs may aid in the diagnosis of a transphyseal distal humerus fracture. Surgical management is most commonly performed with the aid of an arthrogram. Closed reduction and percutaneous pinning techniques similar to those used for supracondylar humerus fractures are employed. Cubitus varus caused by a malunion, osteonecrosis of the medial condyle, or growth arrest is the most common complication encountered in the treatment of transphyseal distal humerus fractures. A corrective lateral closing wedge osteotomy can be performed to restore a nearly normal carrying angle.

  15. Dislocation pinning effects on fracture behavior: Atomistic and dislocation dynamics simulations (United States)

    Noronha, S. J.; Farkas, D.


    We introduce an approach in which results from atomistic simulations are combined with discrete dislocation dynamics simulations of crack-tip plasticity. The method is used to study the effects of dislocation pinning due to grain boundaries or secondary particles on the fracture behavior of aluminum. We find that the fracture resistance is reduced with decreasing pinning distance. The results show that the pinning of the dislocations causes a net decrease in the shear stress projected on the slip plane, preventing further dislocation emission. Semibrittle cleavage occurs after a certain number of dislocations is emitted.



    Zurek, A; G. Gray


    An investigation of the stress-strain response as a function of strain rate, spall strength, and dynamic fracture behavior of pure W, W-26Re, W-Ni- Fe and W-Ni-Fe-Co has been performed. Spall strength measurements, obtained in symmetric-impact tests, showed an increase in spall strength from 0.4 GPa for pure tungsten to 3.8 GPa for 90W-7Ni-3Fe. Concurrent with the increase in spall strength was a change in fracture mode from cleavage (for pure W) to a mixture of transgranular and intergranula...

  17. Cleavage of model substrates by archaeal RNase P: role of protein cofactors in cleavage-site selection. (United States)

    Sinapah, Sylvie; Wu, Shiying; Chen, Yu; Pettersson, B M Fredrik; Gopalan, Venkat; Kirsebom, Leif A


    RNase P is a catalytic ribonucleoprotein primarily involved in tRNA biogenesis. Archaeal RNase P comprises a catalytic RNase P RNA (RPR) and at least four protein cofactors (RPPs), which function as two binary complexes (POP5•RPP30 and RPP21• RPP29). Exploiting the ability to assemble a functional Pyrococcus furiosus (Pfu) RNase P in vitro, we examined the role of RPPs in influencing substrate recognition by the RPR. We first demonstrate that Pfu RPR, like its bacterial and eukaryal counterparts, cleaves model hairpin loop substrates albeit at rates 90- to 200-fold lower when compared with cleavage by bacterial RPR, highlighting the functionally comparable catalytic cores in bacterial and archaeal RPRs. By investigating cleavage-site selection exhibited by Pfu RPR (±RPPs) with various model substrates missing consensus-recognition elements, we determined substrate features whose recognition is facilitated by either POP5•RPP30 or RPP21•RPP29 (directly or indirectly via the RPR). Our results also revealed that Pfu RPR + RPP21•RPP29 displays substrate-recognition properties coinciding with those of the bacterial RPR-alone reaction rather than the Pfu RPR, and that this behaviour is attributable to structural differences in the substrate-specificity domains of bacterial and archaeal RPRs. Moreover, our data reveal a hierarchy in recognition elements that dictates cleavage-site selection by archaeal RNase P.

  18. A Rare Nasal Bone Fracture: Anterior Nasal Spine Fracture

    Directory of Open Access Journals (Sweden)

    Egemen Kucuk


    Full Text Available Anterior nasal spine fractures are a quite rare type of nasal bone fractures. Associated cervical spine injuries are more dangerous than the nasal bone fracture. A case of the anterior nasal spine fracture, in a 18-year-old male was presented. Fracture of the anterior nasal spine, should be considered in the differential diagnosis of the midface injuries and also accompanying cervical spine injury should not be ignored.

  19. Subtask 12D3: Fracture properties of V-5Cr-5Ti Alloy

    Energy Technology Data Exchange (ETDEWEB)

    Li, H.; Hamilton, M.L.; Jones, R.H. [Pacific Northwest Lab., Richland, WA (United States)


    The purpose of this research is to investigate the effect of heat treatment on microstructure and fracture toughness of a V-5Cr-5Ti alloy in the range -50-100{degrees}C. Fracture toughness and impact tests were performed on a V-5Cr-5Ti alloy. Specimens annealed at 1125{degrees}C for 1 h and furnace cooled in a vacuum of 1.33 x 10{sup -5} Pa were brittle at room temperature (RT) and experienced a mixture of intergranular and cleavage fracture. Fracture toughness (J{sub IQ}) at RT was 52 kJ/m{sup 2} and the impact fracture energy (IFE) was 6 J. The IFE at -100{degrees}C was only 1 J. While specimens exhibited high fracture toughness at 100{degrees}C (J{sub IQ} is 485 kj/m{sup 2}), fracture was a mixture of dimple and intergranular failure, with intergranular fracture making up 40% of the total fracture surface. The ductile to brittle transition temperature (DBTT) was estimated to be about 20{degrees}C. When some specimens were given an additional annealing at 890{degrees}C for 24 h, they became very ductile at RT and fractured by microvoid coalescence. The J{sub IQ} value increased from 52 kJ/m{sup 2} to {approximately}1100 kJ/m{sup 2}. The impact test failed to fracture specimens at RT due to a large amount of plastic deformation. 7 refs., 1 fig., 6 tabs.

  20. Synthesis and enzymatic cleavage of dual-ligand quantum dots

    Energy Technology Data Exchange (ETDEWEB)

    Sewell, Sarah L. [Department of Biomedical Engineering, Vanderbilt University, Nashville, TN (United States); Giorgio, Todd D., E-mail: [Department of Biomedical Engineering, Vanderbilt University, Nashville, TN (United States); Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN (United States)


    Site directed therapy promises to minimize treatment-limiting systemic effects associated with cytotoxic agents that have no specificity for pathologic tissues. One general strategy is to target cell surface receptors uniquely presented on particular tissues. Highly specific in vivo targeting of an emerging neoplasm through a single molecular recognition mechanism has not generally been successful. Nonspecific binding and specific binding to non-target cells compromise the therapeutic index of small molecule, ubiquitous cancer targeting ligands. In this work, we have designed and fabricated a nanoparticle (NP) construct that could potentially overcome the current limitations of targeted in vivo delivery. Quantum dots (QDs) were functionalized with a poly(ethylene glycol) (PEG) modified to enable specific cleavage by matrix metalloprotease-7 (MMP-7). The QDs were further functionalized with folic acid, a ligand for a cell surface receptor that is overexpressed in many tumors, but also expressed in some normal tissues. The nanomolecular construct is designed so that the PEG initially conceals the folate ligand and construct binding to cells is inhibited. MMP-7 activated peptide cleavage and subsequent unmasking of the folate ligand occurs only near tumor tissue, resulting in a proximity activated (PA) targeting system. QDs functionalized with both the MMP-7 cleavable substrate and folic acid were successfully synthesized and characterized. The proteolytic capability of the dual ligand QD construct was quantitatively assessed by fluorometric analysis and compared to a QD construct functionalized with only the PA ligand. The dual ligand PA nanoparticles studied here exhibit significant susceptibility to cleavage by MMP-7 at physiologically relevant conditions. The capacity to autonomously convert a biopassivated nanostructure to a tissue-specific targeted delivery agent in vivo represents a paradigm change for site-directed therapies.

  1. Carotenoid-cleavage activities of crude enzymes from Pandanous amryllifolius. (United States)

    Ningrum, Andriati; Schreiner, Matthias


    Carotenoid degradation products, known as norisoprenoids, are aroma-impact compounds in several plants. Pandan wangi is a common name of the shrub Pandanus amaryllifolius. The genus name 'Pandanus' is derived from the Indonesian name of the tree, pandan. In Indonesia, the leaves from the plant are used for several purposes, e.g., as natural colorants and flavor, and as traditional treatments. The aim of this study was to determine the cleavage of β-carotene and β-apo-8'-carotenal by carotenoid-cleavage enzymes isolated from pandan leaves, to investigate dependencies of the enzymatic activities on temperature and pH, to determine the enzymatic reaction products by using Headspace Solid Phase Microextraction Gas Chromatography/Mass Spectrophotometry (HS-SPME GC/MS), and to investigate the influence of heat treatment and addition of crude enzyme on formation of norisoprenoids. Crude enzymes from pandan leaves showed higher activity against β-carotene than β-apo-8'-carotenal. The optimum temperature of crude enzymes was 70°, while the optimum pH value was 6. We identified β-ionone as the major volatile reaction product from the incubations of two different carotenoid substrates, β-carotene and β-apo-8'-carotenal. Several treatments, e.g., heat treatment and addition of crude enzymes in pandan leaves contributed to the norisoprenoid content. Our findings revealed that the crude enzymes from pandan leaves with carotenoid-cleavage activity might provide a potential application, especially for biocatalysis, in natural-flavor industry.

  2. Geothermal Ultrasonic Fracture Imager

    Energy Technology Data Exchange (ETDEWEB)

    Patterson, Doug [Baker-Hughes Oilfield Operation Inc., Houston, TX (United States); Leggett, Jim [Baker-Hughes Oilfield Operation Inc., Houston, TX (United States)


    The Geothermal Ultrasonic Fracture Imager project has a goal to develop a wireline ultrasonic imager that is capable of operating in temperatures up to 300°C (572°F) and depths up to 10 km (32,808 ft). This will address one of the critical needs in any EGS development of understanding the hydraulic flow paths in the reservoir. The ultrasonic imaging is well known in the oil and gas industry as one of the best methods for fracture evaluation; providing both high resolution and complete azimuthal coverage of the borehole. This enables fracture detection and characterization, both natural and induced, providing information as to their location, dip direction and dip magnitude. All of these factors are critical to fully understand the fracture system to enable the optimization of the thermal drainage through injectors and producers in a geothermal resource.

  3. Paediatric talus fracture.

    LENUS (Irish Health Repository)

    Byrne, Ann-Maria


    Paediatric talus fractures are rare injuries resulting from axial loading of the talus against the anterior tibia with the foot in dorsiflexion. Skeletally immature bone is less brittle, with higher elastic resistance than adult bone, thus the paediatric talus can sustain higher forces before fractures occur. However, displaced paediatric talus fractures and those associated with high-energy trauma have been associated with complications including avascular necrosis, arthrosis, delayed union, neurapraxia and the need for revision surgery. The authors present the rare case of a talar neck fracture in a skeletally immature young girl, initially missed on radiological review. However, clinical suspicion on the part of the emergency physician, repeat examination and further radiographic imaging revealed this rare paediatric injury.

  4. Clavicle Fracture (Broken Collarbone) (United States)

    ... Bahk MS, Kuhn JE, Galatz LM, Connor PM, Williams GR: Acromioclavicular and sternoclavicular injuries and cla- vicular, ... Orthopaedic Surgeons. .org Clavicle Fracture cont. Rehabilitation Specific exercises will help restore movement and strengthen your shoulder. ...

  5. Fracture Mechanics of Concrete

    DEFF Research Database (Denmark)

    Ulfkjær, Jens Peder

    Chapter 1 Chapter l contains the introduction to this thesis. The scope of the thesis is partly to investigate different numerical and analytical models based on fracture mechanical ideas, which are able to predict size effects, and partly to perform an experimental investigation on high-strength......Chapter 1 Chapter l contains the introduction to this thesis. The scope of the thesis is partly to investigate different numerical and analytical models based on fracture mechanical ideas, which are able to predict size effects, and partly to perform an experimental investigation on high......-strength concrete. Chapter 2 A description of the factors which influence the strength and cracking of concrete and high strength concrete is made. Then basic linear fracture mechanics is outlined followed by a description and evaluation of the models used to describe concrete fracture in tension. The chapter ends...

  6. Kinetics of acid-catalyzed cleavage of cumene hydroperoxide. (United States)

    Levin, M E; Gonzales, N O; Zimmerman, L W; Yang, J


    The cleavage of cumene hydroperoxide, in the presence of sulfuric acid, to form phenol and acetone has been examined by adiabatic calorimetry. As expected, acid can catalyze cumene hydroperoxide reaction at temperatures below that of thermally-induced decomposition. At elevated acid concentrations, reactivity is also observed at or below room temperature. The exhibited reactivity behavior is complex and is significantly affected by the presence of other species (including the products). Several reaction models have been explored to explain the behavior and these are discussed.

  7. Cleavage of desmin by cysteine proteases: Calpains and cathepsin B

    DEFF Research Database (Denmark)

    Baron, Caroline; Jacobsen, S.; Purslow, P.P.


    The intermediate filament protein, desmin, was purified from pork longissimus dorsi and incubated with either P-calpain, m-calpain or cathepsin B. Proteolysis of desmin was followed using SDS-PAGE and Western blotting. After incubation of desmin with the proteases, cleavage sites on the desmin...... a sequential C-terminal degradation pattern characteristic of this dipeptylpeptidase. The substrate primary structure was not found to be essential for regulation of the proteolytic activity of the cysteine peptidases studied. However, the degradation patterns obtained imply that calpains are involved...

  8. Fracture Behavior under Impact. (United States)


    discussed for the different loading rates ob- tai ned . 1. Introduction In static fracture mechanics crack tip stress intensity factors can easi- - ly...deviation to the left or to the right hand side of the original crack path was observed. Herrmann [151 speculated that this behavior results from stress...Materials’ Draft 2c, American Society for Testing and Materials, Philadelphia, .. ,-- 1980. 15. Herrmann , G., "Dynamic Fracture of Beams in Bending

  9. Relative permeability through fractures

    Energy Technology Data Exchange (ETDEWEB)

    Diomampo, Gracel, P.


    The mechanism of two-phase flow through fractures is of importance in understanding many geologic processes. Currently, two-phase flow through fractures is still poorly understood. In this study, nitrogen-water experiments were done on both smooth and rough parallel plates to determine the governing flow mechanism for fractures and the appropriate methodology for data analysis. The experiments were done using a glass plate to allow visualization of flow. Digital video recording allowed instantaneous measurement of pressure, flow rate and saturation. Saturation was computed using image analysis techniques. The experiments showed that gas and liquid phases flow through fractures in nonuniform separate channels. The localized channels change with time as each phase path undergoes continues breaking and reforming due to invasion of the other phase. The stability of the phase paths is dependent on liquid and gas flow rate ratio. This mechanism holds true for over a range of saturation for both smooth and rough fractures. In imbibition for rough-walled fractures, another mechanism similar to wave-like flow in pipes was also observed. The data from the experiments were analyzed using Darcy's law and using the concept of friction factor and equivalent Reynold's number for two-phase flow. For both smooth- and rough-walled fractures a clear relationship between relative permeability and saturation was seen. The calculated relative permeability curves follow Corey-type behavior and can be modeled using Honarpour expressions. The sum of the relative permeabilities is not equal one, indicating phase interference. The equivalent homogeneous single-phase approach did not give satisfactory representation of flow through fractures. The graphs of experimentally derived friction factor with the modified Reynolds number do not reveal a distinctive linear relationship.

  10. Atomistic simulations of fracture

    Energy Technology Data Exchange (ETDEWEB)

    Farkas, D. [Virginia Polytechnic Inst. and State Univ., Blacksburg, VA (United States). Dept. of Materials Science and Engineering


    Embedded atom interaction potentials are used to simulate the atomistic aspects of the fracture process. Simulations are presented for the behavior of cracks in pure metals and intermetallics, near the Griffith condition. The materials considered include Fe, Cu, Ni as well as Fe, Ni, Co, and Ti aluminides. The work focuses on the comparative study of fracture behavior in the different materials. The role of the atomic relaxation at the crack tip and of lattice trapping phenomena is analyzed.

  11. A Fracture Probability Competition Mechanism of Stress Corrosion Cracking

    Institute of Scientific and Technical Information of China (English)

    Yanliang HUANG


    The stress corrosion cracking (SCC) of austenitic stainless steel was studied via polarization,slow strain rate and scanning electron microscope (SEM) techniques. Many SCC mechanisms have been proposed in which hydrogen embrittlement and passive film rupture-repassivation theories are generally accepted, but they can hardly explain the SCC mechanism of austenitic stainless steel in acidic chloride solution adequately, because the steel is in active dissolution state and cathodic polarization can prevent it from occurring. Our experiment shows that the anodic current increases the creep rate and decreases the plastic strength of the material on single smooth specimen as well as at the SCC crack tip. The fractured surface was characterized as brittle cleavage, while the surface crack of smooth specimen was almost vertical to the tensile strength, which can confirm that the cracks were caused by tensile stresses. A fracture probability competition mechanism of SCC was proposed on the basis of the experimental results combined with the viewpoint of ductile-brittle fracture competition. When the anodic dissolution current is increased to a certain degree, the probability of fracture by tensile stress will exceed that by shear stress, and the brittle fracture will occur. The proposed SCC mechanism can not only explain the propagation of SCC cracks but can explain the crack initiation as well. The strain on the surface distributes unevenly when a smooth specimen is deformed, so does the anodic current distribution. The crack will initiate at a point where the anodic current density is large enough to cause the material at a specific point to fracture in brittle manner.

  12. Subduction of fracture zones (United States)

    Constantin Manea, Vlad; Gerya, Taras; Manea, Marina; Zhu, Guizhi; Leeman, William


    Since Wilson proposed in 1965 the existence of a new class of faults on the ocean floor, namely transform faults, the geodynamic effects and importance of fracture zone subduction is still little studied. It is known that oceanic plates are characterized by numerous fracture zones, and some of them have the potential to transport into subduction zones large volumes of water-rich serpentinite, providing a fertile water source for magma generated in subduction-related arc volcanoes. In most previous geodynamic studies, subducting plates are considered to be homogeneous, and there is no clear indication how the subduction of a fracture zone influences the melting pattern in the mantle wedge and the slab-derived fluids distribution in the subarc mantle. Here we show that subduction of serpentinized fracture zones plays a significant role in distribution of melt and fluids in the mantle wedge above the slab. Using high-resolution tree-dimensional coupled petrological-termomechanical simulations of subduction, we show that fluids, including melts and water, vary dramatically in the region where a serpentinized fracture zone enters into subduction. Our models show that substantial hydration and partial melting tend to concentrate where fracture zones are being subducted, creating favorable conditions for partially molten hydrous plumes to develop. These results are consistent with the along-arc variability in magma source compositions and processes in several regions, as the Aleutian Arc, the Cascades, the Southern Mexican Volcanic Arc, and the Andean Southern Volcanic Zone.

  13. [Subtrochanteric femoral fractures]. (United States)

    Ulmar, B; Simon, S; Eschler, A; Mittlmeier, T


    Subtrochanteric femoral fractures are proximal femoral fractures which are located between the trochanter minor and an area of 3 cm below the minor trochanter on the femoral shaft. About 10-15% of all proximal femoral fractures correspond to this fracture site. Elderly or geriatric patients are generally affected and the injury is often the result of a fall in the home, while high-energy trauma is the cause in a small group of generally younger patients. Clinical evaluation of the affected extremity shows disability of axial weight-bearing and pain during compression and rotation of the hip joint. Basic diagnostics include conventional x-rays of the injured femur in the anterior-posterior and lateral planes. These subtrochanteric femoral fractures are almost always treated surgically due to the inherent high degree of instability. The main goals of surgical intervention are to achieve anatomic fracture reduction and primary full weight-bearing stability of the corresponding leg. Intramedullary interlocking nails are used for primary treatment, while extramedullary implants are often used in revision surgery. Early mobilization and intensive respiratory exercises are necessary to prevent early postoperative complications.


    Energy Technology Data Exchange (ETDEWEB)

    Subhash Shah


    Hydraulic fracturing technology has been successfully applied for well stimulation of low and high permeability reservoirs for numerous years. Treatment optimization and improved economics have always been the key to the success and it is more so when the reservoirs under consideration are marginal. Fluids are widely used for the stimulation of wells. The Fracturing Fluid Characterization Facility (FFCF) has been established to provide the accurate prediction of the behavior of complex fracturing fluids under downhole conditions. The primary focus of the facility is to provide valuable insight into the various mechanisms that govern the flow of fracturing fluids and slurries through hydraulically created fractures. During the time between September 30, 1992, and March 31, 2000, the research efforts were devoted to the areas of fluid rheology, proppant transport, proppant flowback, dynamic fluid loss, perforation pressure losses, and frictional pressure losses. In this regard, a unique above-the-ground fracture simulator was designed and constructed at the FFCF, labeled ''The High Pressure Simulator'' (HPS). The FFCF is now available to industry for characterizing and understanding the behavior of complex fluid systems. To better reflect and encompass the broad spectrum of the petroleum industry, the FFCF now operates under a new name of ''The Well Construction Technology Center'' (WCTC). This report documents the summary of the activities performed during 1992-2000 at the FFCF.

  15. Prevention of hip fractures. (United States)

    Meunier, P J


    For a 50-year old Caucasian woman today, the risk of a hip fracture over her remaining life-time is about 17%. Tomorrow the situation will clearly be worse because the continuous increase in life expectancy will cause a three-fold increase in worldwide fracture incidence over the next 60 years. Through diagnostic bone mass measurements at the hip and assessment of biochemical parameters, a great deal has been learned in recent years about reduction of hip fracture risk. Preventive strategies are based on prevention of falls, use of hip protectors, and prevention of bone fragility. The latter includes the optimization of peak bone mass during childhood, postmenopausal estrogen replacement therapy, and also late prevention consisting in reversing senile secondary hyperparathyroidism, which plays an important role in the decrease of skeletal strength. This secondary hyperparathyroidism, which results from both vitamin D insufficiency and low calcium intake, is preventable with vitamin D3 and calcium supplements. They have recently been shown capable of providing effective prevention of hip fractures in elderly women living in nursing homes, with a reduction of about 25% in the number of hip fractures noted in a 3-year controlled study in 3,270 women (intention-to-treat analysis). In conclusion, it is never too early to reduce the risk of osteoporosis and never too late to prevent hip fractures.

  16. Fracture toughness of graphene. (United States)

    Zhang, Peng; Ma, Lulu; Fan, Feifei; Zeng, Zhi; Peng, Cheng; Loya, Phillip E; Liu, Zheng; Gong, Yongji; Zhang, Jiangnan; Zhang, Xingxiang; Ajayan, Pulickel M; Zhu, Ting; Lou, Jun


    Perfect graphene is believed to be the strongest material. However, the useful strength of large-area graphene with engineering relevance is usually determined by its fracture toughness, rather than the intrinsic strength that governs a uniform breaking of atomic bonds in perfect graphene. To date, the fracture toughness of graphene has not been measured. Here we report an in situ tensile testing of suspended graphene using a nanomechanical device in a scanning electron microscope. During tensile loading, the pre-cracked graphene sample fractures in a brittle manner with sharp edges, at a breaking stress substantially lower than the intrinsic strength of graphene. Our combined experiment and modelling verify the applicability of the classic Griffith theory of brittle fracture to graphene. The fracture toughness of graphene is measured as the critical stress intensity factor of and the equivalent critical strain energy release rate of 15.9 J m(-2). Our work quantifies the essential fracture properties of graphene and provides mechanistic insights into the mechanical failure of graphene.

  17. Importance of greenstick lamina fractures in low lumbar burst fractures (United States)

    Ersozlu, S.; Aydinli, U.


    Lumbar burst fractures (L3–L5) represent a small percentage of all spinal fractures. The treatment of fractures involving the lumbar spine has been controversial. Lamina fractures may be complete or of the greenstick type. Dural tears and nerve root entrapment may accompany these lamina fractures. The aim of this retrospective study was to determine the incidence of dural tear in patients who had lumbar burst fractures with greenstick lamina fractures and the importance of these lamina fractures when choosing the optimum treatment. Twenty-six patients with 28 lumbar burst fractures were treated from 1995 through 2002. The average follow-up was 60 months (range 32–110 months). The male to female ratio was 21:5 and the mean age was 37 years (17–64). Dural tear was detected in seven (25%) out of 28 burst fractures. The functional outcome of the entire study group was assessed using the Smiley-Webster Scale. Good to excellent results were obtained in 24 (92%) of 26 patients. Lumbar burst fractures with greenstick lamina fractures occur mostly in the L2–L4 area. In the surgical treatment, any reduction manoeuvre will close the fracture and crush the entrapped neural elements. Therefore, it may be better to explore the greenstick lamina fracture whether there is any neural entrapment or not, before any reduction manoeuvre is attempted. PMID:16501977

  18. Mechanical strength and analysis of fracture of titanium joining submitted to laser and tig welding

    Directory of Open Access Journals (Sweden)

    Ana Cláudia Gabrielli Piveta


    Full Text Available This study compared the tensile strength and fracture mechanism of tungsten inert gas (TIG welds in cylindrical rods of commercially pure titanium (cp Ti with those of laser welds and intact samples. Thirty dumbbell-shaped samples were developed by using brass rods as patterns. The samples were invested in casings, subjected to thermal cycles, and positioned in a plasma arc welding machine under argon atmosphere and vacuum, and titanium was injected under vacuum/pressure. The samples were X-rayed to detect possible welding flaws and randomly assigned to three groups to test the tensile strength and the fracture mechanism: intact, laser welding, and TIG welding. The tensile test results were investigated using ANOVA, which indicated that the samples were statistically similar. The fracture analysis showed that the cpTi samples subjected to laser welding exhibited brittle fracture and those subjected to TIG welding exhibited mixed brittle/ductile fracture with a predominance of ductile fracture with the presence of microcavities and cleavage areas. Intact samples presented the characteristic straightening in the fracture areas, indicating the ductility of the material.

  19. Quantitative characterization of the fracture surface of Si single crystals by confocal microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Xin, Y.B.; Hsia, K.J.; Lange, D.A. [Univ. of Illinois, Urbana, IL (United States)


    Experiments are conducted to study the dislocation nucleation conditions at the crack tip in {l_brace}110{r_brace}<110> oriented Si single crystals. Specimens with surface cracks are first statically loaded at elevated temperatures for a prolonged period of time to initiate and move dislocations away from the crack tip, then cooled down to room temperature and loaded to fracture to measure the fracture toughness. Fractographic analysis of the fracture surfaces is performed. Distinct wavy patterns on the fracture surface at the initial cleavage crack front are observed, which is attributed to the existence of local mixed mode 1/mode 3 stresses resulting from the inhomogeneous dislocation activity. Confocal microscopy is employed to quantify the fracture surface roughness. The results show that the increase of fracture toughness is directly associated with the increased area of the rough surface, which is characterized by the roughness number or the fractal dimension increment. The results also demonstrate that dislocation nucleation can occur only at discrete sites. The spacing between these dislocation nucleation sources is of the order of 1 {micro}m. A simple model is developed for the relationship between the fracture toughness and the surface roughness parameters, which is in good agreement with the experimental results.

  20. CT of pelvic fractures

    Energy Technology Data Exchange (ETDEWEB)

    Falchi, Marco E-mail:; Rollandi, Gian Andrea


    Although magnetic resonance imaging has become the dominant modality for cross-sectional musculo-skeletal imaging, the widespread availability, speed, and versatility of computed tomography (CT) continue to make it a mainstay of emergency room (ER) diagnostic imaging. Pelvic ring and acetabular fractures occur as the result of significant trauma secondary to either a motor vehicle accident or a high-velocity fall. These injuries are correlated with significant morbidity and mortality, both from the complications of pelvic ring fractures and from commonly associated injuries. The most commonly used classification of pelvic and acetabular fractures has been based on conventional radiographs that are, in the majority of cases, sufficient to determine the type of injury. However, because of the complexity of pelvic and acetabular fractures, precise pathological anatomy is not easily demonstrated by routine radiographs and in many cases details of fractures are not visible. Moreover, the insufficient co-operation of the patient or the difficulty of maintaining special positions can be overcome by using computed tomography. Spiral computed tomography provides information regarding the extent of the fractures and is complementary to radiography for ascertaining the spatial arrangement of fracture fragments. Spiral computed tomography is an effective tool for understanding complex fracture patterns, particularly when combined with multi-planar reconstruction two-dimensional (MPR 2D) reformatted images or three-dimensional images (3D) images. Including these techniques of reconstruction in routine pelvic imaging protocols can change management in a significant number of cases. Subtle fractures, particularly those oriented in the axial plane, are better seen on MPR images or 3D volume-rendered images. Complex injuries can be better demonstrated with 3D volume-rendered images, and complicated spatial information about the relative positions of fracture fragments can be easily

  1. Cleavage by MALT1 induces cytosolic release of A20. (United States)

    Malinverni, Claire; Unterreiner, Adeline; Staal, Jens; Demeyer, Annelies; Galaup, Marion; Luyten, Marcel; Beyaert, Rudi; Bornancin, Frédéric


    The MALT1 paracaspase has arginine-directed proteolytic activity. A20 is a dual ubiquitin-editing enzyme involved in termination of NF-κB signaling. Upon T- or B-cell receptor engagement human (h) A20 is cleaved by MALT1 after arginine 439, yielding an N-terminal fragment (hA20p50) and a C-terminal one (hA20p37). The hA20p50 fragment has never been detected directly, thus limiting insight into the functional consequences of MALT1-mediated cleavage of A20. Here, various antibodies were tested, including newly generated hA20p50 and hA20p37 specific antibodies, leading to detection of the hA20p50 fragment produced after MALT1-mediated cleavage of ectopically expressed as well as endogenous A20 proteins. The properties of both A20 fragments, generated upon co-expression with a constitutively active MALT1 protein, were further studied by sub-cellular fractionation and fluorescence microscopy. In contrast to full-length A20 which is particulate and insoluble, we found hA20p50 to be soluble and readily released into the cytosol whereas hA20p37 was partially soluble, thus suggesting loss of compartmentalization as a possible mechanism for MALT1-mediated dampening of A20 function.

  2. piRNA-directed cleavage of meiotic transcripts regulates spermatogenesis. (United States)

    Goh, Wee Siong Sho; Falciatori, Ilaria; Tam, Oliver H; Burgess, Ralph; Meikar, Oliver; Kotaja, Noora; Hammell, Molly; Hannon, Gregory J


    MIWI catalytic activity is required for spermatogenesis, indicating that piRNA-guided cleavage is critical for germ cell development. To identify meiotic piRNA targets, we augmented the mouse piRNA repertoire by introducing a human meiotic piRNA cluster. This triggered a spermatogenesis defect by inappropriately targeting the piRNA machinery to mouse mRNAs essential for germ cell development. Analysis of such de novo targets revealed a signature for pachytene piRNA target recognition. This enabled identification of both transposable elements and meiotically expressed protein-coding genes as targets of native piRNAs. Cleavage of genic targets began at the pachytene stage and resulted in progressive repression through meiosis, driven at least in part via the ping-pong cycle. Our data support the idea that meiotic piRNA populations must be strongly selected to enable successful spermatogenesis, both driving the response away from essential genes and directing the pathway toward mRNA targets that are regulated by small RNAs in meiotic cells.


    Directory of Open Access Journals (Sweden)

    Paul Ander


    Full Text Available A new pulp fibre testing procedure called the HCl method was used to compare different spruce and pine fibres and mixtures of these fibres to calculate number of fibre cleavages in dislocations and other weak points. This method was compared with treatment of softwood kraft pulp fibres using different cellulase mixtures. The HCl method can distinguish between mill- and laboratory-made softwood kraft pulp fibres from the same wood batch. The sugar release is characterized by xylose and other hemicellulose sugars and little glucose. This is in contrast to cellulases, which despite strong fibre cleavage, did not distinguish between mill- and laboratory-made pulp fibres and released large amounts of glucose from the fibres. Hemicellulose degradation by HCl and deep penetration of the acid into the primary and secondary fibre cell walls at 80°C seems to be of major importance for the differentiation between mill and laboratory pulp fibres. Cellulases, in contrast, act mostly on the fibre surfaces, and deep penetration only takes place in amorphous regions of dislocations.

  4. Surveillance and Cleavage of Eukaryotic tRNAs

    Directory of Open Access Journals (Sweden)

    Cyrille Megel


    Full Text Available Beyond their central role in protein synthesis, transfer RNAs (tRNAs have many other crucial functions. This includes various roles in the regulation of gene expression, stress responses, metabolic processes and priming reverse transcription. In the RNA world, tRNAs are, with ribosomal RNAs, among the most stable molecules. Nevertheless, they are not eternal. As key elements of cell function, tRNAs need to be continuously quality-controlled. Two tRNA surveillance pathways have been identified. They act on hypo-modified or mis-processed pre-tRNAs and on mature tRNAs lacking modifications. A short overview of these two pathways will be presented here. Furthermore, while the exoribonucleases acting in these pathways ultimately lead to complete tRNA degradation, numerous tRNA-derived fragments (tRFs are present within a cell. These cleavage products of tRNAs now potentially emerge as a new class of small non-coding RNAs (sncRNAs and are suspected to have important regulatory functions. The tRFs are evolutionarily widespread and created by cleavage at different positions by various endonucleases. Here, we review our present knowledge on the biogenesis and function of tRFs in various organisms.

  5. Atomistic Simulations of Nanotube Fracture

    CERN Document Server

    Belytschko, T; Schatz, G; Ruoff, R S


    The fracture of carbon nanotubes is studied by atomistic simulations. The fracture behavior is found to be almost independent of the separation energy and to depend primarily on the inflection point in the interatomic potential. The rangle of fracture strians compares well with experimental results, but predicted range of fracture stresses is marketly higher than observed. Various plausible small-scale defects do not suffice to bring the failure stresses into agreement with available experimental results. As in the experiments, the fracture of carbon nanotubes is predicted to be brittle. The results show moderate dependence of fracture strength on chirality.

  6. CT classification of acetabular fractures

    Energy Technology Data Exchange (ETDEWEB)

    Marincek, B.; Porcellini, B.; Robotti, G.


    The contribution of computed tomography (CT) in classifying acetabular fractures was analysed retrospectively in 33 cases. CT and plain radiography classification agreed in 27 cases (82%). CT revealed more extensive fractures in 6 patients (thereof 5 patients with associated fractures). In 10 patients (thereof 9 patients with associated fractures) CT showed intraarticular fragments; radiographically intraarticular fragments were seen only in 2 patients and suspected in 4. CT is of considerable aid in defining the fracture pattern. It should be used mainly in patients with radiographically difficult interpretable associated fractures in order to assess preoperatively the weight-bearing part of the acetabulum, the degree of displacement and the presence of intraarticular fragments.

  7. [Humeral shaft fractures]. (United States)

    Schittko, A


    Since Lorenz Böhler postulated in his 1964 summary with the title "Against the operative treatment of fresh humeral shaft fractures" that the operative treatment is the exception in the therapy of humeral fractures times have changed. In the last years a conservative treatment of a humeral fracture is the exception and only used after straight indications. The operative therapy nowadays is the gold standard because of the development of new intramedullar and rotation stable implants in addition to the classical osteosynthesis with the plate. But even the external fixator for primary stabilisation in polytrauma patients or as rescue procedure after complications should be in repertory of every orthopedic surgeon. Attention should be put on the avoidance of primary and the correct treatment of secondary nerval lesions, esp. of the radial nerve. Here we are tending to the operative revision of the nerve in indistinct cases. In the treatment of the seldom humeral shaft fracture of the child conservative treatment is to prefer; in complications a resolute shift to a final operative stabilisation of the fracture is necessary.

  8. A single molecule assay for measuring site-specific DNA cleavage. (United States)

    Gambino, Stefano; Mousley, Briana; Cathcart, Lindsay; Winship, Janelle; Loparo, Joseph J; Price, Allen C


    Sequence-specific DNA cleavage is a key step in a number of genomic transactions. Here, we report a single-molecule technique that allows the simultaneous measurement of hundreds of DNAs, thereby collecting significant statistics in a single experiment. Microbeads are tethered with single DNA molecules in a microfluidic channel. After the DNA cleavage reaction is initiated, the time of cleavage of each DNA is recorded using video microscopy. We demonstrate the utility of our method by measuring the cleavage kinetics of NdeI, a type II restriction endonuclease.

  9. Fracture-Flow-Enhanced Solute Diffusion into Fractured Rock

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Yu-Shu; Ye, Ming; Sudicky, E.A.


    We propose a new conceptual model of fracture-flow-enhanced matrix diffusion, which correlates with fracture-flow velocity, i.e., matrix diffusion enhancement induced by rapid fluid flow within fractures. According to the boundary-layer or film theory, fracture flow enhanced matrix diffusion may dominate mass-transfer processes at fracture-matrix interfaces, because rapid flow along fractures results in large velocity and concentration gradients at and near fracture-matrix interfaces, enhancing matrix diffusion at matrix surfaces. In this paper, we present a new formulation of the conceptual model for enhanced fracture-matrix diffusion, and its implementation is discussed using existing analytical solutions and numerical models. In addition, we use the enhanced matrix diffusion concept to analyze laboratory experimental results from nonreactive and reactive tracer breakthrough tests, in an effort to validate the new conceptual model.

  10. Transstyloid, transscaphoid, transcapitate fracture: a variant of scaphocapitate fractures.

    LENUS (Irish Health Repository)

    Burke, Neil G


    Transstyloid, transscaphoid, transcapitate fractures are uncommon. We report the case of a 28-year-old man who sustained this fracture following direct trauma. The patient was successfully treated by open reduction internal fixation of the scaphoid and proximal capitate fragment, with a good clinical outcome at 1-year follow-up. This pattern is a new variant of scaphocapitate fracture as involves a fracture of the radial styloid as well.

  11. DEM Particle Fracture Model

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Boning [Univ. of Colorado, Boulder, CO (United States); Herbold, Eric B. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Homel, Michael A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Regueiro, Richard A. [Univ. of Colorado, Boulder, CO (United States)


    An adaptive particle fracture model in poly-ellipsoidal Discrete Element Method is developed. The poly-ellipsoidal particle will break into several sub-poly-ellipsoids by Hoek-Brown fracture criterion based on continuum stress and the maximum tensile stress in contacts. Also Weibull theory is introduced to consider the statistics and size effects on particle strength. Finally, high strain-rate split Hopkinson pressure bar experiment of silica sand is simulated using this newly developed model. Comparisons with experiments show that our particle fracture model can capture the mechanical behavior of this experiment very well, both in stress-strain response and particle size redistribution. The effects of density and packings o the samples are also studied in numerical examples.

  12. Vertebral Geometry Parameters Can Predict Fractures

    Directory of Open Access Journals (Sweden)

    P Tofighi


    Conclusion: Vertebral fractures are common fractures in postmenopausal women. There was a correlation between verte¬bral height and fractures. Vertebral geometric parameters especially height T score can be used for fracture screening.

  13. Enzymic Pathways for Formation of Carotenoid Cleavage Products (United States)

    Fleischmann, Peter; Zorn, Holger

    Degraded carotenoids (apocarotenoids, norisoprenoids) have been a subject of intensive research for several decades. From the perspective of human physiology and nutrition, the retinoids, acting as vitamins, signalling molecules, and visual pigments, attracted the greatest attention (Chapters 15 and 16). Plant scientists, however, detected a wealth of different apocarotenoids, presumably derived by the excentric cleavage of carotenoids in various species, the plant hormone abscisic acid (1, Scheme 6) being the best-investigated example. With the onset of fruit ripening, flower opening or senescence of green tissues, carotenoids are degraded oxidatively to smaller, volatile compounds. The natural biological functions of the reaction products are outlined in Chapter 15. As many of these apocarotenoids act as potent flavour compounds, food chemists and flavourists worldwide have investigated meticulously their structural and sensory properties. Many aspects of carotenoid metabolites and breakdown products as aroma compounds are presented in a comprehensive book [1].

  14. Dinitrogen cleavage and hydrogenation by a trinuclear titanium polyhydride complex. (United States)

    Shima, Takanori; Hu, Shaowei; Luo, Gen; Kang, Xiaohui; Luo, Yi; Hou, Zhaomin


    Both the Haber-Bosch and biological ammonia syntheses are thought to rely on the cooperation of multiple metals in breaking the strong N≡N triple bond and forming an N-H bond. This has spurred investigations of the reactivity of molecular multimetallic hydrides with dinitrogen. We report here the reaction of a trinuclear titanium polyhydride complex with dinitrogen, which induces dinitrogen cleavage and partial hydrogenation at ambient temperature and pressure. By (1)H and (15)N nuclear magnetic resonance, x-ray crystallographic, and computational studies of some key reaction steps and products, we have determined that the dinitrogen (N2) reduction proceeds sequentially through scission of a N2 molecule bonded to three Ti atoms in a μ-η(1):η(2):η(2)-end-on-side-on fashion to give a μ2-N/μ3-N dinitrido species, followed by intramolecular hydrogen migration from Ti to the μ2-N nitrido unit.

  15. Regulation of DNA Replication in Early Embryonic Cleavages

    Directory of Open Access Journals (Sweden)

    Chames Kermi


    Full Text Available Early embryonic cleavages are characterized by short and highly synchronous cell cycles made of alternating S- and M-phases with virtually absent gap phases. In this contracted cell cycle, the duration of DNA synthesis can be extraordinarily short. Depending on the organism, the whole genome of an embryo is replicated at a speed that is between 20 to 60 times faster than that of a somatic cell. Because transcription in the early embryo is repressed, DNA synthesis relies on a large stockpile of maternally supplied proteins stored in the egg representing most, if not all, cellular genes. In addition, in early embryonic cell cycles, both replication and DNA damage checkpoints are inefficient. In this article, we will review current knowledge on how DNA synthesis is regulated in early embryos and discuss possible consequences of replicating chromosomes with little or no quality control.

  16. Cleavage of an amide bond by a ribozyme (United States)

    Dai, X.; De Mesmaeker, A.; Joyce, G. F.; Miller, S. L. (Principal Investigator)


    A variant form of a group I ribozyme, optimized by in vitro evolution for its ability to catalyze magnesium-dependent phosphoester transfer reactions involving DNA substrates, also catalyzes the cleavage of an unactivated alkyl amide when that linkage is presented in the context of an oligodeoxynucleotide analog. Substrates containing an amide bond that joins either two DNA oligos, or a DNA oligo and a short peptide, are cleaved in a magnesium-dependent fashion to generate the expected products. The first-order rate constant, kcat, is 0.1 x 10(-5) min-1 to 1 x 10(-5) min-1 for the DNA-flanked substrates, which corresponds to a rate acceleration of more than 10(3) as compared with the uncatalyzed reaction.

  17. [Supracondylar fractures in children]. (United States)

    Petrov, N; Gucev, S; Kirkov, Lj; Dajljevik, S; Ruso, B


    In the Department of Pediatric surgery, during the last ten years, 190 patients with supracondylar fractures (second and third degree, according to Bauman's classification) have been treated. The operation was performed in only 5% of all hospitalized cases. There were only one patient with neurological and vascular complications in the early stage, but without any complications in the late stage. The presented cases showed a high percentage of flexion type of fractures. The conservative treatment by a reposition has given the most satisfactory results.

  18. Fractured Petroleum Reservoirs

    Energy Technology Data Exchange (ETDEWEB)

    Firoozabadi, Dr. Abbas


    In this report the results of experiments of water injection in fractured porous media comprising a number of water-wet matrix blocks are reported for the first time. The blocks experience an advancing fracture-water level (FWL). Immersion-type experiments are performed for comparison; the dominant recovery mechanism changed from co-current to counter-current imbibition when the boundary conditions changed from advancing FWL to immersion-type. Single block experiments of co-current and counter-current imbibition was performed and co-current imbibition leads to more efficient recovery was found.

  19. Complications of mandibular fractures. (United States)

    Zweig, Barry E


    Before any definitive treatment of mandibular fractures, the patient needs to be evaluated for more potentially life-threatening injuries. Complications can and do occur with treatment of mandibular fractures and can occur during any of the phases of treatment. The development of an accurate diagnosis and appropriate treatment plan is vital in achieving optimal success and decreasing complications. Knowledge of the anatomy and the principles of bone healing is also an important factor in preventing complications. To limit long-term untoward effects, complications should be recognized early and the appropriate treatment should be started before a minor complication becomes a complex one that is more difficult to manage.

  20. A designer bleomycin with significantly improved DNA cleavage activity. (United States)

    Huang, Sheng-Xiong; Feng, Zhiyang; Wang, Liyan; Galm, Ute; Wendt-Pienkowski, Evelyn; Yang, Dong; Tao, Meifeng; Coughlin, Jane M; Duan, Yanwen; Shen, Ben


    The bleomycins (BLMs) are used clinically in combination with a number of other agents for the treatment of several types of tumors, and the BLM, etoposide, and cisplatin treatment regimen cures 90-95% of metastatic testicular cancer patients. BLM-induced pneumonitis is the most feared, dose-limiting side effect of BLM in chemotherapy, which can progress into lung fibrosis and affect up to 46% of the total patient population. There have been continued efforts to develop new BLM analogues in the search for anticancer drugs with better clinical efficacy and lower lung toxicity. We have previously cloned and characterized the biosynthetic gene clusters for BLMs from Streptomyces verticillus ATCC15003, tallysomycins from Streptoalloteichus hindustanus E465-94 ATCC31158, and zorbamycin (ZBM) from Streptomyces flavoviridis SB9001. Comparative analysis of the three biosynthetic machineries provided the molecular basis for the formulation of hypotheses to engineer novel analogues. We now report engineered production of three new analogues, 6'-hydroxy-ZBM, BLM Z, and 6'-deoxy-BLM Z and the evaluation of their DNA cleavage activities as a measurement for their potential anticancer activity. Our findings unveiled: (i) the disaccharide moiety plays an important role in the DNA cleavage activity of BLMs and ZBMs, (ii) the ZBM disaccharide significantly enhances the potency of BLM, and (iii) 6'-deoxy-BLM Z represents the most potent BLM analogue known to date. The fact that 6'-deoxy-BLM Z can be produced in reasonable quantities by microbial fermentation should greatly facilitate follow-up mechanistic and preclinical studies to potentially advance this analogue into a clinical drug.

  1. Ultrarapid mutation detection by multiplex, solid-phase chemical cleavage

    Energy Technology Data Exchange (ETDEWEB)

    Rowley, G.; Saad, S.; Giannelli, F.; Green, P.M. [Guy`s & St. Thomas`s Hospitals, London (United Kingdom)


    The chemical cleavage of mismatches in heteroduplexes formed by probe and test DNA detects and locates any sequence change in long DNA segments ({approximately}1.8 kb), and its efficiency has been well tested in the analysis of both average (e.g., coagulation factor IX) and large, complex genes (e.g., coagulation factor VIII and dystrophin). In the latter application RT/PCR products allow the examination of all essential sequences of the gene in a minimum number of reactions. We use two specific chemical reactants (hydroxylamine and osmium tetroxide) and piperidine cleavage of the above procedure to develop a very fast mutation screening method. This is based on: (1) 5{prime} or internal fluorescent labeling to allow concurrent screening of three to four DNA fragments and (2) solid-phase chemistry to use a microliter format and reduce the time required for the procedure, from amplification of sequence to gel loading inclusive, to one person-working-day. We test the two variations of the method, one entailing 5{prime} labeling of probe DNA and the other uniform labeling of both probe and target DNA, by detecting 114 known hemophilia B (coagulation factor IX) mutations and by analyzing 129 new patients. Uniform labeling of both probe and target DNA prior to formation of the heteroduplexes leads to almost twofold redundancy in the ability to detect mutations. Alternatively, the latter procedure may offer very efficient though less than 100% screening for sequence changes with only hydroxylamine. The full method with two chemical reactions (hydroxylamine and osmium tetroxide) should allow one person to screen with virtually 100% accuracy more than 300 kb of sequence in three ABI 373 gels in 1 day. 26 refs., 7 figs., 1 tab.

  2. C-S bond cleavage by a polyketide synthase domain. (United States)

    Ma, Ming; Lohman, Jeremy R; Liu, Tao; Shen, Ben


    Leinamycin (LNM) is a sulfur-containing antitumor antibiotic featuring an unusual 1,3-dioxo-1,2-dithiolane moiety that is spiro-fused to a thiazole-containing 18-membered lactam ring. The 1,3-dioxo-1,2-dithiolane moiety is essential for LNM's antitumor activity, by virtue of its ability to generate an episulfonium ion intermediate capable of alkylating DNA. We have previously cloned and sequenced the lnm gene cluster from Streptomyces atroolivaceus S-140. In vivo and in vitro characterizations of the LNM biosynthetic machinery have since established that: (i) the 18-membered macrolactam backbone is synthesized by LnmP, LnmQ, LnmJ, LnmI, and LnmG, (ii) the alkyl branch at C-3 of LNM is installed by LnmK, LnmL, LnmM, and LnmF, and (iii) leinamycin E1 (LNM E1), bearing a thiol moiety at C-3, is the nascent product of the LNM hybrid nonribosomal peptide synthetase (NRPS)-acyltransferase (AT)-less type I polyketide synthase (PKS). Sulfur incorporation at C-3 of LNM E1, however, has not been addressed. Here we report that: (i) the bioinformatics analysis reveals a pyridoxal phosphate (PLP)-dependent domain, we termed cysteine lyase (SH) domain (LnmJ-SH), within PKS module-8 of LnmJ; (ii) the LnmJ-SH domain catalyzes C-S bond cleavage by using l-cysteine and l-cysteine S-modified analogs as substrates through a PLP-dependent β-elimination reaction, establishing l-cysteine as the origin of sulfur at C-3 of LNM; and (iii) the LnmJ-SH domain, sharing no sequence homology with any other enzymes catalyzing C-S bond cleavage, represents a new family of PKS domains that expands the chemistry and enzymology of PKSs and might be exploited to incorporate sulfur into polyketide natural products by PKS engineering.

  3. Distal Radius Fracture (Broken Wrist) (United States)

    .org Distal Radius Fracture (Broken Wrist) Page ( 1 ) The radius is the larger of the two bones of the forearm. The ... the distal end. A fracture of the distal radius occurs when the area of the radius near ...

  4. Colles wrist fracture – aftercare (United States)

    ... . Prawer A. Radius and ulna fractures. In: Eiff MP, Hatch RL, eds. Fracture Management for Primary Care . 3rd ed. Philadelphia, PA: Elsevier Saunders; 2011:chap ...

  5. Effect of heat treatment on microstructure and fracture toughness of a V-5Cr-5Ti alloy

    Energy Technology Data Exchange (ETDEWEB)

    Li, H.; Hamilton, M.L.; Jones, R.H. [Pacific Northwest Lab., Richland, WA (United States)


    The purpose of this research is to investigate the effect of heat treatment on microstructure and fracture toughness in the range of {minus}50 to 100{degrees}C for a V-5Cr-5Ti alloy. Fracture toughness and impact tests were performed on a V-5Cr-5Ti alloy. Specimens annealed at 1125{degree}C for 1 h and furnace cooled in a vacuum of 1.33 x 10{sup {minus}5} Pa were brittle at room temperature and experienced a mixture of intergranular and cleavage fracture. The ductile to brittle transition temperature was estimated to be about 20{degree}C. When some specimens were given an additional annealing at 890{degree}C for 24 h, they became very ductile at room temperature and fractured by microvoid coalescence.

  6. Modeling the Ductile Brittle Fracture Transition in Reactor Pressure Vessel Steels using a Cohesive Zone Model based approach

    Energy Technology Data Exchange (ETDEWEB)

    Pritam Chakraborty; S. Bulent Biner


    Fracture properties of Reactor Pressure Vessel (RPV) steels show large variations with changes in temperature and irradiation levels. Brittle behavior is observed at lower temperatures and/or higher irradiation levels whereas ductile mode of failure is predominant at higher temperatures and/or lower irradiation levels. In addition to such temperature and radiation dependent fracture behavior, significant scatter in fracture toughness has also been observed. As a consequence of such variability in fracture behavior, accurate estimates of fracture properties of RPV steels are of utmost importance for safe and reliable operation of reactor pressure vessels. A cohesive zone based approach is being pursued in the present study where an attempt is made to obtain a unified law capturing both stable crack growth (ductile fracture) and unstable failure (cleavage fracture). The parameters of the constitutive model are dependent on both temperature and failure probability. The effect of irradiation has not been considered in the present study. The use of such a cohesive zone based approach would allow the modeling of explicit crack growth at both stable and unstable regimes of fracture. Also it would provide the possibility to incorporate more physical lower length scale models to predict DBT. Such a multi-scale approach would significantly improve the predictive capabilities of the model, which is still largely empirical.

  7. Microcracks and Overpressure- Induced Fractures

    Institute of Scientific and Technical Information of China (English)

    Ahmed M. Al - QAHTANI


    The microfractures and natural fractures studies have a great significance in the hydrocarbon accumulation exploration and can be a good supporter for wide geophysical study on the major structures. This paper is a brief review on microcracks and overpressure- induced fracture. It is to discuss different views on the mechanism of fractures in the subsurface of the earth.

  8. Tensile deformation and fracture micromorphology of an Fe-28Al-4Cr-0.1Ce alloy

    Energy Technology Data Exchange (ETDEWEB)

    Karlik, M.; Siegl, J. [Czech Tech. Univ., Prague (Czech Republic). Dept. of Mater.; Kratochvil, P.; Janecek, M. [Department of Metal Physics, Charles University, Ke Karlovu 5, 121 16 2, Prague (Czech Republic); Vodickova, V. [Department of Materials, TU Liberec, Halkova 6, 461 17, Liberec (Czech Republic)


    Fracture and mechanical properties of a vacuum cast and hot extruded Fe-28Al-4Cr-0.1Ce (at.%) alloy were studied as a function of temperature and strain rate. The tensile deformation tests were carried out at temperatures ranging from 20 to 700 C, at strain rates of {proportional_to}10{sup -4} s{sup -1} and {proportional_to}10{sup -2} s{sup -1}. The effects of strain rate and testing temperature are well recognized in the fractographic features. At room temperature the main fracture mechanism is intergranular decohesion with a certain proportion of transgranular cleavage. With increasing temperature the proportion of transgranular cleavage and ductile dimple fracture gradually increase at the expense of intergranular decohesion. The plastic deformation at each testing temperature is more developed at lower strain rate. The changes in the micromorphology of fracture correlate better with reduction of area than with elongation to fracture. Room temperature ductility of 6.5 and 8.6%, was found for the strain rate of {proportional_to}10{sup -4} s{sup -1} and {proportional_to}10{sup -2} s{sup -1}, respectively. (orig.)

  9. Injection through fractures

    Energy Technology Data Exchange (ETDEWEB)

    Johns, R.A.


    Tracer tests are conducted in geothermal reservoirs as an aid in forecasting thermal breakthrough of reinjection water. To interpret tracer tests, mathematical models have been developed based on the various transport mechanisms in these highly fractured reservoirs. These tracer flow models have been applied to interpret field tests. The resulting matches between the model and field data were excellent and the model parameters were used to estimate reservoir properties. However, model fitting is an indirect process and the model's ability to estimate reservoir properties cannot be judged solely on the quality of the match between field data and model predictions. The model's accuracy in determining reservoir characteristics must be independently verified in a closely controlled environment. In this study, the closely controlled laboratory environment was chosen to test the validity and accuracy of tracer flow models developed specifically for flow in fractured rocks. The laboratory tracer tests were performed by flowing potassium iodide (KI) through artificially fractured core samples. The tracer test results were then analyzed with several models to determine which best fit the measured data. A Matrix Diffusion model was found to provide the best match of the tracer experiments. The core properties, as estimated by the Matrix Diffusion model parameters generated from the indirect matching process, were then determined. These calculated core parameters were compared to the measured core properties and were found to be in agreement. This verifies the use of the Matrix Diffusion flow model in estimating fracture widths from tracer tests.

  10. Fracture Toughness Characterization

    Directory of Open Access Journals (Sweden)

    Manuel Beltrán Z


    Full Text Available This paper addresses the fracture toughness ( , or also known as critical stress intensity Factor, according to conditions of Lineal Elastic Fracture Mechanics (LEFM. The characterization of the mechanical properties in tensile and fracture toughness of structural steel pipes API-5L used in hydrocarbons transportation was performed. For fracture toughness, the material was tested through fatigue crack propagation on standardized compact specimen (CT according to ASTM E-399 norm. A thickness (B equal to and a crack size (a equal to 0.5w were used. With the porpoise of establishing the adequate conditions at the crack tip, the specimens were subjected to fatigue pre-cracking by application of repeated cycles of load in tensile-tensile and constant load amplitude with a load ratio of R = 0.1. The experimental Compliance method was used based on data obtained from load vs. Crack Mouth Opening Displacement (CMOD. The results show a Stress Intensity factor of 35.88 MPa√m for a 25 mm crack size specimen. The device used for testing is a MTS-810 machine with capacity of 100KN and 6 kHz sampling rate, which meets the conditions of the ASTM E-399 standard. The cracking susceptibility of steel is influenced by the size, morphology and distribution of non-metallic inclusions, thermochemical interaction with the environment and microstructure.

  11. Oblique Axis Body Fracture

    DEFF Research Database (Denmark)

    Takai, Hirokazu; Konstantinidis, Lukas; Schmal, Hagen


    type" fracture pattern. The first patient was treated conservatively with cervical spine immobilization in a semirigid collar. However, gross displacement was noted at the 6-week follow-up visit. The second patient was therefore treated operatively by C1-C3/4 posterior fusion and the course...... for this injury and suggest early operative stabilization....

  12. Fracture design modelling

    Energy Technology Data Exchange (ETDEWEB)

    Crichlow, H.B.; Crichlow, H.B. (ed.)


    A design tool is discussed whereby the various components that enter the design process of a hydraulic fracturing job are combined to provide a realistic appraisal of a stimulation job in the field. An interactive computer model is used to solve the problem numerically to obtain the effects of various parameters on the overall behavior of the system.

  13. Neglected hangman fracture

    Directory of Open Access Journals (Sweden)

    Sudhir Kumar Srivastava


    Full Text Available Acute management of hangman fracture is well described; however the surgical management of neglected hangman fracture has not been described in literature. We report the surgical management of an untreated hangman′s fracture. A 30-year-old male had fallen from a tree 12 weeks back. Patient presented with cervical myelopathy and restricted neck movements. Radiographs and computed tomography (CT scan revealed fracture of pars interarticularis of axis with Grade III C2-C3 spondylolisthesis with localized kyphosis of 33°. Gentle reduction under general anesthesia (GA failed to improve the alignment. Patient was operated in three stages in a single setting. In Stage I, release of contracted anterior structures and C2-C3 discectomy was done in supine position followed by C2-C3 posterior fixation and fusion in Stage II. C2-C3 interbody bone grafting and anterior plating completed the third stage. C2-C3 interbody fusion was seen at 5 months and a CT scan at 18 months postoperative confirmed fusion and maintenance of alignment. The satisfactory outcome in our patient leads us to believe that anterior-posterior-anterior is the appropriate surgical approach for treatment of such patients.

  14. Proximal femoral fractures

    DEFF Research Database (Denmark)

    Palm, Henrik; Teixidor, Jordi


    searched the homepages of the national heath authorities and national orthopedic societies in West Europe and found 11 national or regional (in case of no national) guidelines including any type of proximal femoral fracture surgery. RESULTS: Pathway consensus is outspread (internal fixation for un...

  15. Fracture toughness testing of V-4Cr-4Ti at 25{degrees}C and -196{degrees}C

    Energy Technology Data Exchange (ETDEWEB)

    Li, H.X.; Kurtz, R.J. [Pacific Northwest National Lab., Richland, WA (United States)


    Measurements of the fracture toughness of the production-scale heat (832665) of V-4Cr-4Ti have been performed at 25{degrees}C and {minus}196{degrees}C using compact tension (CT) specimens. Test specimens were vacuum annealed at either 1000{degrees}C for 1 hour (HT1) or 1050{degrees}C for two hours (HT2). Specimens given the HT1 treatment were annealed after final machining, whereas the HT2 specimens received the 1050{degrees}C anneal at Teledyne Wah Chang prior to final machining. Following machining HT2 specimens were then vacuum annealed at 180{degrees}C for two hours to remove hydrogen. Specimens treated using HT1 had a partially recrystallized microstructure and those treated using HT2 had a fully recrystallized microstructure. The fracture toughness at 25{degrees}C was determined by J-integral tests and at {minus}196{degrees}C by ASTM E 399 type tests. Toughness values obtained at {minus}196{degrees}C were converted to J-integral values for comparison to the 25{degrees}C data. The 25{degrees}C fracture toughness was very high with none of the specimens giving valid results per ASTM criteria. Specimens fractured by microvoid coalescence. The fracture toughness at {minus}196{degrees}C was much lower than that at 25{degrees}C and the fracture surface showed predominantly cleavage features. The present results show a transition from ductile to brittle behavior with decreasing test temperature which is not observed from one-third scale Charpy impact tests. The fracture toughness at {minus}196{degrees}C was still quite high, however, at about 75 kJ/m{sup 2}. Delaminations in planes normal to the thickness direction were seen at both test temperatures. Fracture surfaces inside the delaminations exhibited nearly 100% cleavage facets. The cause of the brittle delaminations was not determined, but will be a subject for further investigation.

  16. Investigation of the fracture mechanics of boride composites (United States)

    Kaufman, L.; Clougherty, E. V.; Nesor, H.


    Fracture energies of WC-6Co, Boride 5 (ZrB2+SiC), Boride 8(ZrB2+SiC+C) and Boride 8-M2(ZrB2+SiC+C) were measured by slow bend and impact tests of notched charpy bars. Cobalt bonded tungsten carbide exhibited impact energies of 0.76 ft-lb or 73.9 in-lb/square inch. Boride 5 and the Boride 8 exhibit impact energies one third and one quarter of that observed for WC-6Co comparing favorably with measurements for SiC and Si3N4. Slow bend-notched bar-fracture energies for WC-6Co were near 2.6 in-lb/square inch or 1/20 the impact energies. Slow bend energies for Boride 8-M2, Boride 8 and Boride 5 were 58%, 42% and 25% of the value observed for WC-6Co. Fractograph showed differences for WC-6Co where slow bend testing resulted in smooth transgranular cleavage while samples broken by impact exhibited intergranular failures. By contrast the boride fractures showed no distinction based on testing method. Fabrication studies were conducted to effect alteration of the boride composites by alloying and introduction of graphite cloth.

  17. Carbon-carbon bond cleavage in activation of the prodrug nabumetone

    DEFF Research Database (Denmark)

    Varfaj, Fatbardha; Zulkifli, Siti N A; Park, Hyoung-Goo;


    Carbon-carbon bond cleavage reactions are catalyzed by, among others, lanosterol 14-demethylase (CYP51), cholesterol side-chain cleavage enzyme (CYP11), sterol 17β-lyase (CYP17), and aromatase (CYP19). Because of the high substrate specificities of these enzymes and the complex nature of their su...

  18. Oxidative cleavage of benzylic C-N bonds under metal-free conditions. (United States)

    Gong, Jin-Long; Qi, Xinxin; Wei, Duo; Feng, Jian-Bo; Wu, Xiao-Feng


    An interesting procedure for the oxidative cleavage of benzylic C-N bonds has been developed. Using TBAI as the catalyst and H2O2 as the oxidant, various benzylamines were transformed into their corresponding aromatic aldehydes in moderate to good yields. Notably, this is the first example of an oxidative cleavage of benzylic C-N bonds under metal-free conditions.

  19. Unexpected tolerance of alpha-cleavage of the prion protein to sequence variations.

    Directory of Open Access Journals (Sweden)

    José B Oliveira-Martins

    Full Text Available The cellular form of the prion protein, PrP(C, undergoes extensive proteolysis at the alpha site (109K [see text]H110. Expression of non-cleavable PrP(C mutants in transgenic mice correlates with neurotoxicity, suggesting that alpha-cleavage is important for PrP(C physiology. To gain insights into the mechanisms of alpha-cleavage, we generated a library of PrP(C mutants with mutations in the region neighbouring the alpha-cleavage site. The prevalence of C1, the carboxy adduct of alpha-cleavage, was determined for each mutant. In cell lines of disparate origin, C1 prevalence was unaffected by variations in charge and hydrophobicity of the region neighbouring the alpha-cleavage site, and by substitutions of the residues in the palindrome that flanks this site. Instead, alpha-cleavage was size-dependently impaired by deletions within the domain 106-119. Almost no cleavage was observed upon full deletion of this domain. These results suggest that alpha-cleavage is executed by an alpha-PrPase whose activity, despite surprisingly limited sequence specificity, is dependent on the size of the central region of PrP(C.

  20. Chromium(VI) reduction by catechol(amine)s results in DNA cleavage in vitro

    DEFF Research Database (Denmark)

    Pattison, D I; Davies, Michael Jonathan; Levina, A;


    ) or 4-tert-butylcatechol (5) do not damage DNA. The Cr(VI)/catechol(amine) reactions have been studied at low added H(2)O(2) concentrations, which lead to enhanced DNA cleavage with 1 and induce DNA cleavage with 4. The Cr(V) and organic intermediates generated by the reactions of Cr(VI) with 1 or 4...

  1. Comparative and phylogenetic perspectives of the cleavage process in tailed amphibians. (United States)

    Desnitskiy, Alexey G; Litvinchuk, Spartak N


    The order Caudata includes about 660 species and displays a variety of important developmental traits such as cleavage pattern and egg size. However, the cleavage process of tailed amphibians has never been analyzed within a phylogenetic framework. We use published data on the embryos of 36 species concerning the character of the third cleavage furrow (latitudinal, longitudinal or variable) and the magnitude of synchronous cleavage period (up to 3-4 synchronous cell divisions in the animal hemisphere or a considerably longer series of synchronous divisions followed by midblastula transition). Several species from basal caudate families Cryptobranchidae (Andrias davidianus and Cryptobranchus alleganiensis) and Hynobiidae (Onychodactylus japonicus) as well as several representatives from derived families Plethodontidae (Desmognathus fuscus and Ensatina eschscholtzii) and Proteidae (Necturus maculosus) are characterized by longitudinal furrows of the third cleavage and the loss of synchrony as early as the 8-cell stage. By contrast, many representatives of derived families Ambystomatidae and Salamandridae have latitudinal furrows of the third cleavage and extensive period of synchronous divisions. Our analysis of these ontogenetic characters mapped onto a phylogenetic tree shows that the cleavage pattern of large, yolky eggs with short series of synchronous divisions is an ancestral trait for the tailed amphibians, while the data on the orientation of third cleavage furrows seem to be ambiguous with respect to phylogeny. Nevertheless, the midblastula transition, which is characteristic of the model species Ambystoma mexicanum (Caudata) and Xenopus laevis (Anura), might have evolved convergently in these two amphibian orders.

  2. Coronavirus 3CL(pro) proteinase cleavage sites: Possible relevance to SARS virus pathology

    DEFF Research Database (Denmark)

    Kiemer, Lars; Lund, Ole; Brunak, Søren


    such as the cystic fibrosis transmembrane conductance regulator ( CFTR), transcription factors CREB-RP and OCT-I, and components of the ubiquitin pathway. Conclusions: Our prediction method NetCorona predicts coronavirus cleavage sites with high specificity and several potential cleavage candidates were identified...

  3. Altered cleavage patterns in human tripronuclear embryos and their association to fertilization method

    DEFF Research Database (Denmark)

    Joergensen, Mette Warming; Agerholm, Inge; Hindkjaer, Johnny


    PURPOSE: To analyze the cleavage patterns in dipronuclear (2PN) and tripronuclear (3PN) embryos in relation to fertilization method. METHOD: Time-lapse analysis. RESULTS: Compared to 2PN, more 3PN IVF embryos displayed early cleavage into 3 cells (p cell...... stage (p cell divisions within the cleavage cycles differed between the two groups. In contrast......, the completion of the 1st, 2nd, and 3rd cleavage cycle was delayed, but with a similar division pattern for 3PN ICSI compared with the 2PN ICSI embryos. 3PN, more often than 2PN ICSI embryos, displayed early cleavage into 3 cells (p = 0.03) and arrested development from the compaction stage and onwards (p = 0...

  4. Real-time monitoring of DNAzyme cleavage process using fluorescent assay

    Institute of Scientific and Technical Information of China (English)

    Xiang Xian Meng; Xiao Hai Yang; Ke Min Wang; Wei Hong Tan; Qiu Ping Guo


    Detection of deoxyribozyme (DNAzyme) cleavage process usually needs complex and time-consuming radial labeling, gel electrophoresis and autoradiography. This paper reported an approach to detect DNAzyme cleavage process in real time using a fluorescence probe. The probe was employed as DNAzyme substrate to convert directly the cleavage information into fluorescence signal in real time. Compared with traditional approach, this non-isotope method not only brought a convenient means to monitor the DNAzyme cleavage reaction, but also offered abundant dynamic data for choosing potential gene therapeutic agents. It provides a new tool for DNAzyme research, as well as a new insight into research on human disease diagnosis. Based on this method, 8-17deoxyribozyme (8-17DNAzyme) against hepatitis C virus RNA (HCV-RNA) was designed and the cleavage process was studied in real time.

  5. Ultrasensitive monitoring of ribozyme cleavage product using molecular-beacon-ligation system

    Institute of Scientific and Technical Information of China (English)

    MENG XiangXian; TANG ZhiWen; WANG KeMin; TAN WeiHong; YANG XiaoHai; LI Jun; GUO QiuPing


    This paper reports a new approach to detect ribozyme cleavage product based on the molecular- beacon-ligation system. The molecular beacon, designed in such a way that one-half of its loop is complementary to ribozyme cleavage product, is used to monitor ligation process of RNA/DNA complex in a homogeneous solution and to convert directly cleavage product information into fluorescence signal. The method need not label ribozyme and ribozyme substrate, which is fast, simple and ultrasensitive for detection of cleavage product. Detection limit of the assay is 0.05 nmol/L. The cleavage product of hammerhead ribozyme against hepatitis C virus RNA (HCV-RNA) was detected perfectly based on this assay. Owing to its ultrasensitivity, excellent specificity, convenience and fidelity, this method might hold out great promise in ribozyme reaction and ribozyme gene therapy.

  6. Site Specificity of Cleavage of DSP-PP by BMP1 (United States)

    Yang, Robert T.; Lim, Glendale L.; Yee, Colin T.; Fuller, Robert S.; Ritchie, Helena H.


    Bone morphogenic protein 1 (BMP1), a metalloproteinase, is known to cleave a wide variety of extracellular matrix proteins, suggesting that a consensus substrate cleavage amino acid sequence might exist. However, while such a consensus sequence has been proposed based on P4 to P4′ (i.e., the four amino acids flanking either side of the BMP1 cleavage site; P4P3P2P1|P1′P2′P3′P4′) sequence homologies between two BMP1 substrates, dentin matrix protein 1 and dentin sialoprotein phosphophoryn (DSP-PP) (i.e., xMQx | DDP), no direct testing has so far been attempted. Using an Sf9 cell expression system, we have been able to produce large amounts of uncleaved DSP-PP,. Point mutations introduced into this recombinant DSP-PP were then tested for their affects on DSP-PP cleavage by either Sf9 endogenous tolloid-related protein 1 (TLR-1) or by its human homolog, BMP1. Here we have measured DSP-PP cleavage efficiencies after modifications based on P4-P4′ sequence comparisons with dentin matrix protein 1, as well as for prolysyl oxidase and chordin, two other BMP1 substrates. Our results demonstrate that any mutations within or outside of the DSP-PP P4 to P4′ cleavage site can block, impair or accelerate DSP-PP cleavage, and suggest that its BMP1 cleavage site is highly conserved in order to regulate its cleavage efficiency, possibly with additional assistance from its conserved exosites. Thus, BMP1 cleavage cannot be based on a consensus substrate cleavage site. PMID:25158199

  7. Sox11 Reduces Caspase-6 Cleavage and Activity.

    Directory of Open Access Journals (Sweden)

    Elaine Waldron-Roby

    Full Text Available The apoptotic cascade is an orchestrated event, whose final stages are mediated by effector caspases. Regulatory binding proteins have been identified for caspases such as caspase-3, -7, -8, and -9. Many of these proteins belong to the inhibitor of apoptosis (IAP family. By contrast, caspase-6 is not believed to be influenced by IAPs, and little is known about its regulation. We therefore performed a yeast-two-hybrid screen using a constitutively inactive form of caspase-6 for bait in order to identify novel regulators of caspase-6 activity. Sox11 was identified as a potential caspase-6 interacting protein. Sox11 was capable of dramatically reducing caspase-6 activity, as well as preventing caspase-6 self- cleavage. Several regions, including amino acids 117-214 and 362-395 within sox11 as well as a nuclear localization signal (NLS all contributed to the reduction in caspase-6 activity. Furthermore, sox11 was also capable of decreasing other effector caspase activity but not initiator caspases -8 and -9. The ability of sox11 to reduce effector caspase activity was also reflected in its capacity to reduce cell death following toxic insult. Interestingly, other sox proteins also had the ability to reduce caspase-6 activity but to a lesser extent than sox11.

  8. Computational redesign of endonuclease DNA binding and cleavage specificity (United States)

    Ashworth, Justin; Havranek, James J.; Duarte, Carlos M.; Sussman, Django; Monnat, Raymond J.; Stoddard, Barry L.; Baker, David


    The reprogramming of DNA-binding specificity is an important challenge for computational protein design that tests current understanding of protein-DNA recognition, and has considerable practical relevance for biotechnology and medicine. Here we describe the computational redesign of the cleavage specificity of the intron-encoded homing endonuclease I-MsoI using a physically realistic atomic-level forcefield. Using an in silico screen, we identified single base-pair substitutions predicted to disrupt binding by the wild-type enzyme, and then optimized the identities and conformations of clusters of amino acids around each of these unfavourable substitutions using Monte Carlo sampling. A redesigned enzyme that was predicted to display altered target site specificity, while maintaining wild-type binding affinity, was experimentally characterized. The redesigned enzyme binds and cleaves the redesigned recognition site ~10,000 times more effectively than does the wild-type enzyme, with a level of target discrimination comparable to the original endonuclease. Determination of the structure of the redesigned nuclease-recognition site complex by X-ray crystallography confirms the accuracy of the computationally predicted interface. These results suggest that computational protein design methods can have an important role in the creation of novel highly specific endonucleases for gene therapy and other applications.

  9. DNA targeting and cleavage by an engineered metalloprotein dimer. (United States)

    Wong-Deyrup, Siu Wah; Prasannan, Charulata; Dupureur, Cynthia M; Franklin, Sonya J


    Nature has illustrated through numerous examples that protein dimerization has structural and functional advantages. We previously reported the design and characterization of an engineered "metallohomeodomain" protein (C2) based on a chimera of the EF-hand Ca-binding motif and the helix-turn-helix motif of homeodomains (Lim and Franklin in Protein Sci. 15:2159-2165, 2004). This small metalloprotein binds the hard metal ions Ca(II) and Ln(III) and interacts with DNA with modest sequence preference and affinity, yet exhibits only residual DNA cleavage activity. Here we have achieved substantial improvement in function by constructing a covalent dimer of this C2 module (F2) to create a larger multidomain protein. As assayed via fluorescence spectroscopy, this F2 protein binds Ca(II) more avidly (25-fold) than C2 on a per-domain basis; in gel shift selection experiments, metallated F2 exhibits a specificity toward 5'-TAATTA-3' sequences. Finally, Ca(2)F2 cleaves plasmid DNA and generates a linear product in a Ca(II)-dependent way, unlike the CaC2 monomer. To the best of our knowledge this activation of Ca(II) in the context of an EF-hand binding motif is unique and represents a significant step forward in the design of artificial metallonucleases by utilizing biologically significant metal ions.

  10. Diaphanous gene mutation affects spiral cleavage and chirality in snails (United States)

    Kuroda, Reiko; Fujikura, Kohei; Abe, Masanori; Hosoiri, Yuji; Asakawa, Shuichi; Shimizu, Miho; Umeda, Shin; Ichikawa, Futaba; Takahashi, Hiromi


    L-R (left and right) symmetry breaking during embryogenesis and the establishment of asymmetric body plan are key issues in developmental biology, but the onset including the handedness-determining gene locus still remains unknown. Using pure dextral (DD) and sinistral (dd) strains of the pond snail Lymnaea stagnalis as well as its F2 through to F10 backcrossed lines, the single handedness-determining-gene locus was mapped by genetic linkage analysis, BAC cloning and chromosome walking. We have identified the actin-related diaphanous gene Lsdia1 as the strongest candidate. Although the cDNA and derived amino acid sequences of the tandemly duplicated Lsdia1 and Lsdia2 genes are very similar, we could discriminate the two genes/proteins in our molecular biology experiments. The Lsdia1 gene of the sinistral strain carries a frameshift mutation that abrogates full-length LsDia1 protein expression. In the dextral strain, it is already translated prior to oviposition. Expression of Lsdia1 (only in the dextral strain) and Lsdia2 (in both chirality) decreases after the 1-cell stage, with no asymmetric localization throughout. The evolutionary relationships among body handedness, SD/SI (spiral deformation/spindle inclination) at the third cleavage, and expression of diaphanous proteins are discussed in comparison with three other pond snails (L. peregra, Physa acuta and Indoplanorbis exustus). PMID:27708420


    Directory of Open Access Journals (Sweden)

    Deepak Kaladagi


    Full Text Available BACKGROUND: The incidence of humeral fracture has significantly increased during the present years due to the population growth and road traffic, domestic, industrial, automobile accidents & disasters like tsunami, earthquakes, head-on collisions, polytrauma etc. In order to achieve a stable fixation followed by early mobilization, numerous surgical implants have been devised. PURPOSE: The purpose of this study is to analyze the results of intramedullary fixation of proximal 2/3rd humeral shaft fractures using an unreamed interlocking intramedullary nail. INTRODUCTION: In 40 skeletally matured patients with fracture shaft of humerus admitted in our hospital, we used unreamed antegrade interlocking nails. MATERIAL: We carried out a prospective analysis of 40 patients randomly selected between 2001 to 2014 who were operated at JNMC Belgaum, MMC Mysore & Navodaya Medical College, Raichur. All cases were either RTAs, Domestic, Industrial, automobile accidents & also other modes of injury. METHOD: Routine investigations with pre-anaesthetic check-up & good quality X-rays of both sides of humerus was taken. Time of surgery ranged from 5-10 days from the time of admission. Only upper 1/3rd & middle 1/3rd humeral shaft fractures were included in the study. In all the cases antegrade locked unreamed humeral nails were inserted under C-arm. Patient was placed in supine position & the shoulder was kept elevated by placing a sandbag under the scapula. In all patients incision taken from tip of acromion to 3cm over deltoid longitudinally. Postoperatively sling applied with wrist & shoulder movements started after 24 hours. All the patients ranged between the age of 21-50 years. RESULTS: Total 40 patients were operated. Maximum fracture site were in the middle third- 76%, 14% upper 1/3rd. All 40 patients achieved union. The average time of union was 8-10 weeks. All patients regained full range of movements except in few cases, where there was shoulder

  12. Fracture of brittle solids

    CERN Document Server

    Lawn, Brian


    This is an advanced text for higher degree materials science students and researchers concerned with the strength of highly brittle covalent-ionic solids, principally ceramics. It is a reconstructed and greatly expanded edition of a book first published in 1975. The book presents a unified continuum, microstructural and atomistic treatment of modern day fracture mechanics from a materials perspective. Particular attention is directed to the basic elements of bonding and microstructure that govern the intrinsic toughness of ceramics. These elements hold the key to the future of ceramics as high-technology materials--to make brittle solids strong, we must first understand what makes them weak. The underlying theme of the book is the fundamental Griffith energy-balance concept of crack propagation. The early chapters develop fracture mechanics from the traditional continuum perspective, with attention to linear and nonlinear crack-tip fields, equilibrium and non-equilibrium crack states. It then describes the at...

  13. Fracture of sandwiched composites

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Weh-Huei.


    Fracture of a pair of collinear cracks in various materials, such as an isotropic strip, an orthotropic strip, a bonded isotropic adhesive layer, and sandwiched orthotropic layers, is investigated. The crack surfaces are subjected to an arbitrary opening pressure p(x). The problems are formulated in terms of Fredholm integral equation of the second kind by making use the techniques of Fourier transform and finite Hilbert transform. In case of uniform opening pressure p(x)={sigma}, exact expressions for the stress intensity factors and the shape of deformed crack are obtained. Numerical calculations are carried out to study the effects of various boundary geometries and material properties on the fracture of the chosen materials.

  14. Phase Field Fracture Mechanics.

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, Brett Anthony [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)


    For this assignment, a newer technique of fracture mechanics using a phase field approach, will be examined and compared with experimental data for a bend test and a tension test. The software being used is Sierra Solid Mechanics, an implicit/explicit finite element code developed at Sandia National Labs in Albuquerque, New Mexico. The bend test experimental data was also obtained at Sandia Labs while the tension test data was found in a report online from Purdue University.

  15. Tibial shaft fracture

    DEFF Research Database (Denmark)

    Larsen, Peter

    IV also showed a significant worse outcome in 3 of the 5 KOOS subscales compared to a reference population at 12-months follow-up. Moreover, this study showed that increasing difference in muscle strength for knee extension between legs was associated with a decreasing QOL. The results of this thesis...... suggested that regaining pre injured QOL and muscle strength following a tibial shaft fracture takes considerable time....

  16. Haemodynamically Unstable Pelvic Fractures (United States)


    through the pubic symphysis, and posteriorlywith the sacrum forming the sacroiliac (SI) joints (Fig. 1). The SI joints are the strongest in the body...Gardner MJ, Kendoff D, Ostermeier S, et al. Sacroiliac joint compression using an anterior pelvic compressor: a mechanical study in synthetic bone. J...commonly identified at arteriography.35 Posterior fracture along the SI joints may cause disruption of a main iliac trunk, but is rare, occurring less

  17. Double segmental tibial fractures - an unusual fracture pattern

    Directory of Open Access Journals (Sweden)

    Bali Kamal


    Full Text Available 【Abstract】A case of a 50-year-old pedestrian who was hit by a bike and suffered fractures of both bones of his right leg was presented. Complete clinical and radiographic assessment showed double segmental fractures of the tibia and multisegmental fractures of the fibula. Review of the literature revealed that this fracture pattern was unique and only a single case was reported so far. Moreover, we discussed the possible mechanisms which can lead to such an injury. We also discussed the management of segmental tibial fracture and the difficulties encountered with them. This case was managed by modern osteosynthesis tech- nique with a pleasing outcome. Key words: Fracture, bone; Tibia; Fibula; Nails

  18. Fracture Networks in Sea Ice

    Directory of Open Access Journals (Sweden)

    Jonas Nesland Vevatne


    Full Text Available Fracturing and refreezing of sea ice in the Kara sea are investigated using complex networkanalysis. By going to the dual network, where the fractures are nodes and their intersectionslinks, we gain access to topological features which are easy to measure and hence comparewith modeled networks. Resulting network reveal statistical properties of the fracturing process.The dual networks have a broad degree distribution, with a scale-free tail, high clusteringand efficiency. The degree-degree correlation profile shows disassortative behavior, indicatingpreferential growth. This implies that long, dominating fractures appear earlier than shorterfractures, and that the short fractures which are created later tend to connect to the longfractures.The knowledge of the fracturing process is used to construct growing fracture network (GFNmodel which provides insight into the generation of fracture networks. The GFN model isprimarily based on the observation that fractures in sea ice are likely to end when hitting existingfractures. Based on an investigation of which fractures survive over time, a simple model forrefreezing is also added to the GFN model, and the model is analyzed and compared to the realnetworks.

  19. Fractures of the cervical spine

    Directory of Open Access Journals (Sweden)

    Raphael Martus Marcon


    Full Text Available OBJECTIVES: The aim of this study was to review the literature on cervical spine fractures. METHODS: The literature on the diagnosis, classification, and treatment of lower and upper cervical fractures and dislocations was reviewed. RESULTS: Fractures of the cervical spine may be present in polytraumatized patients and should be suspected in patients complaining of neck pain. These fractures are more common in men approximately 30 years of age and are most often caused by automobile accidents. The cervical spine is divided into the upper cervical spine (occiput-C2 and the lower cervical spine (C3-C7, according to anatomical differences. Fractures in the upper cervical spine include fractures of the occipital condyle and the atlas, atlanto-axial dislocations, fractures of the odontoid process, and hangman's fractures in the C2 segment. These fractures are characterized based on specific classifications. In the lower cervical spine, fractures follow the same pattern as in other segments of the spine; currently, the most widely used classification is the SLIC (Subaxial Injury Classification, which predicts the prognosis of an injury based on morphology, the integrity of the disc-ligamentous complex, and the patient's neurological status. It is important to correctly classify the fracture to ensure appropriate treatment. Nerve or spinal cord injuries, pseudarthrosis or malunion, and postoperative infection are the main complications of cervical spine fractures. CONCLUSIONS: Fractures of the cervical spine are potentially serious and devastating if not properly treated. Achieving the correct diagnosis and classification of a lesion is the first step toward identifying the most appropriate treatment, which can be either surgical or conservative.

  20. Fracture-Toughness Analysis in Transition-Temperature Region of Three American Petroleum Institute X70 and X80 Pipeline Steels (United States)

    Shin, Sang Yong; Woo, Kuk Je; Hwang, Byoungchul; Kim, Sangho; Lee, Sunghak


    The fracture toughness in the transition-temperature region of three American Petroleum Institute (API) X70 and X80 pipeline steels was analyzed in accordance with the American Society for Testing and Materials (ASTM) E1921-05 standard test method. The elastic-plastic cleavage fracture toughness ( K Jc ) was determined by three-point bend tests, using precracked Charpy V-notch (PCVN) specimens; the measured K Jc values were then interpreted by the three-parameter Weibull distribution. The fracture-toughness test results indicated that the master curve and the 98 pct confidence curves explained the variation in the measured fracture toughness well. The reference temperatures obtained from the fracture-toughness test and index temperatures obtained from the Charpy impact test were lowest in the X70 steel rolled in the two-phase region, because this steel had smaller effective grains and the lowest volume fraction of hard phases. In this steel, few hard phases led to a higher resistance to cleavage crack initiation, and the smaller effective grain size led to a higher possibility of crack arrest, thereby resulting in the best overall fracture properties. Measured reference temperatures were then comparatively analyzed with the index temperatures obtained from the Charpy impact test, and the effects of microstructures on these temperatures were discussed.

  1. Elastic-plastic fracture mechanics of strength-mismatching

    Energy Technology Data Exchange (ETDEWEB)

    Parks, D.M.; Ganti, S.; McClintock, F.A. [Massachusetts Institute of Technology, Cambridge, MA (United States)


    Approximate solutions to stress-fields are provided for a strength-mismatched interface crack in small-scale yielding (SSY) for non-hardening and low hardening materials. Variations of local deformation intensities, characterized by a J-type contour integral, are proposed. The softer material experiences a higher deformation intensity level, J{sub S}, while the harder material sees a much lower deformation intensity level, J{sub H}, compared to that obtained from the applied J near the respective homogeneous crack-tips. For a low hardening material, the stress fields are obtained by scaling from an elastic/perfectly-plastic problem, based on an effective mismatch, M{sub eff}, which is a function of mismatch, M, and the hardening exponent, n. Triaxial stress build-up is discussed quantitatively in terms of M. The influence of strength-mismatch on cleavage fracture is discussed using Weibull statistics.

  2. Molecular determinants of survival motor neuron (SMN protein cleavage by the calcium-activated protease, calpain.

    Directory of Open Access Journals (Sweden)

    Jennifer L Fuentes

    Full Text Available Spinal muscular atrophy (SMA is a leading genetic cause of childhood mortality, caused by reduced levels of survival motor neuron (SMN protein. SMN functions as part of a large complex in the biogenesis of small nuclear ribonucleoproteins (snRNPs. It is not clear if defects in snRNP biogenesis cause SMA or if loss of some tissue-specific function causes disease. We recently demonstrated that the SMN complex localizes to the Z-discs of skeletal and cardiac muscle sarcomeres, and that SMN is a proteolytic target of calpain. Calpains are implicated in muscle and neurodegenerative disorders, although their relationship to SMA is unclear. Using mass spectrometry, we identified two adjacent calpain cleavage sites in SMN, S192 and F193. Deletion of small motifs in the region surrounding these sites inhibited cleavage. Patient-derived SMA mutations within SMN reduced calpain cleavage. SMN(D44V, reported to impair Gemin2 binding and amino-terminal SMN association, drastically inhibited cleavage, suggesting a role for these interactions in regulating calpain cleavage. Deletion of A188, a residue mutated in SMA type I (A188S, abrogated calpain cleavage, highlighting the importance of this region. Conversely, SMA mutations that interfere with self-oligomerization of SMN, Y272C and SMNΔ7, had no effect on cleavage. Removal of the recently-identified SMN degron (Δ268-294 resulted in increased calpain sensitivity, suggesting that the C-terminus of SMN is important in dictating availability of the cleavage site. Investigation into the spatial determinants of SMN cleavage revealed that endogenous calpains can cleave cytosolic, but not nuclear, SMN. Collectively, the results provide insight into a novel aspect of the post-translation regulation of SMN.

  3. Development of Numerical Analysis Techniques Based on Damage Mechanics and Fracture Mechanics

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Yoon Suk; Lee, Dock Jin; Choi, Shin Beom; Kim, Sun Hye; Cho, Doo Ho; Lee, Hyun Boo [Sungkyunkwan University, Seoul (Korea, Republic of)


    The scatter of measured fracture toughness data and transferability problems among different crack configurations as well as geometry and loading conditions are major obstacles for application of fracture mechanics. To address these issues, recently, concerns on the local approach employing reliable micro-mechanical damage models are being increased again in connection with a progress of computational technology. In the present research, as part of development of fracture mechanical evaluation model for material degradation of reactor pressure boundary, several investigations on fracture behaviors were carried out. Especially, a numerical scheme to determine key parameters consisting both cleavage and ductile fracture estimate models was changed efficiently by incorporating a genetic algorithm. Also, with regard to the well-known master curve, newly reported methods such as bimodal master curve, randomly inhomogeneous master curve and single point estimation were reviewed to deal with homogeneous and inhomogeneous material characteristics. A series of preliminary finite element analyses was conducted to examine the element size effect on micro-mechanical models. Then, a new thickness correction equation was derived from parametric three-dimensional numerical simulations, which was founded on the current test standard, ASTM E1921, but could lead to get more realistic fracture toughness values. As a result, promising modified master curves as well as fracture toughness diagrams to convert data between pre-cracked V-notched and compact tension specimens were generated. Moreover, a user-subroutine in relation to GTN(Gurson-Tvergaard-Needleman) model was made by adopting Hill's 48 yield potential theory. By applying GTN model combined with the subroutine to small punch specimens, the effect of inhomogeneous properties on fracture behaviors of miniature specimens was confirmed. Therefore, it is anticipated that the aforementioned enhanced research results can be

  4. In vitro proteolytic cleavage of Gazdar murine sarcoma virus p65gag.


    Maxwell, S.; Arlinghaus, R B


    Moloney murine leukemia virus, disrupted in concentrations of 0.1 to 0.5% Nonidet P-40, catalyzed the cleavage of p65, the gag gene polyprotein of the Gazdar strain of murine sarcoma virus, into polypeptides with sizes and antigenic determinants of murine leukemia virus-specified p30, p15, pp12, and p10. Cleavage performed in the presence of 0.15% Nonidet P-40 in water yielded polypeptides of approximately 40,000 (P40) and 25,000 (P25) Mr. In vitro cleavage performed in a buffered solution co...

  5. Enzymology of the carotenoid cleavage dioxygenases: reaction mechanisms, inhibition and biochemical roles. (United States)

    Harrison, Peter J; Bugg, Timothy D H


    Carotenoid cleavage dioxygenases (CCDs) are a large family of non-heme iron (II) dependent enzymes. CCDs catalyse the selective oxidative cleavage of carotenoids to produce apocarotenoids. Apocarotenoid derived molecules form important signalling molecules in plants in the form of abscisic acid and strigolactone and in mammals in the form of retinal. Very little is known biochemically about the CCDs and only a handful of CCDs have been biochemically characterised. Mechanistically, debate surrounds whether CCDs utilise a mono or dioxygenase mechanism. Here, we review the biochemical roles of CCDs, discuss the mechanisms by which CCD cleavage is proposed to occur, and discuss recent reports of selective CCD enzyme inhibitors.

  6. Guest-host interactions in the cleavage of phenylphenyl acetates by -cyclodextrin in alkaline medium

    Indian Academy of Sciences (India)

    V Raj; T Chandrakala; K Rajasekaran


    Kinetics of cleavage of phenylphenyl acetates (PPA) and several para-substituted PPAs in basic aqueous sodium carbonate-bicarbonate buffer containing -cyclodextrin (CD) have been studied. The reaction exhibits saturation type kinetics and CD accelerates the rate of cleavage by the formation of 1G : 1H inclusion complex. The kinetic results indicate that aryloxy moiety of PPA is included in the hydrophobic cavity of CD. The overall rate constants for the cleavage of the [CD-ester] complex correlate with the Hammett -constants and Hansch hydrophobicity parameters . At higher concentrations of CD, there is an additional catalysis due to the formation of weak 1G : 2H complex.


    Energy Technology Data Exchange (ETDEWEB)

    Abbas Firoozabadi


    The four chapters that are described in this report cover a variety of subjects that not only give insight into the understanding of multiphase flow in fractured porous media, but they provide also major contribution towards the understanding of flow processes with in-situ phase formation. In the following, a summary of all the chapters will be provided. Chapter I addresses issues related to water injection in water-wet fractured porous media. There are two parts in this chapter. Part I covers extensive set of measurements for water injection in water-wet fractured porous media. Both single matrix block and multiple matrix blocks tests are covered. There are two major findings from these experiments: (1) co-current imbibition can be more efficient than counter-current imbibition due to lower residual oil saturation and higher oil mobility, and (2) tight fractured porous media can be more efficient than a permeable porous media when subjected to water injection. These findings are directly related to the type of tests one can perform in the laboratory and to decide on the fate of water injection in fractured reservoirs. Part II of Chapter I presents modeling of water injection in water-wet fractured media by modifying the Buckley-Leverett Theory. A major element of the new model is the multiplication of the transfer flux by the fractured saturation with a power of 1/2. This simple model can account for both co-current and counter-current imbibition and computationally it is very efficient. It can be orders of magnitude faster than a conventional dual-porosity model. Part II also presents the results of water injection tests in very tight rocks of some 0.01 md permeability. Oil recovery from water imbibition tests from such at tight rock can be as high as 25 percent. Chapter II discusses solution gas-drive for cold production from heavy-oil reservoirs. The impetus for this work is the study of new gas phase formation from in-situ process which can be significantly

  8. New propant schedule in hydralic fracturing

    Energy Technology Data Exchange (ETDEWEB)

    Wang, H.; Fan, C.


    A new proppant schedule is suggested to obtain maximum propping surface area and maximum fracture conductivity near the borehole. The small and middle size sands are suspended in the fracturing fluids under fracturing condition to prop the total fracture surface area created by fracturing. The coarse sands pumped into fracture later deposit in the fracture at the dynamic width near the borehole during fracturing and reach the equilibrium height in the time interval of pumping coarse sands. Thus, fracture conductivity near the borehole is increased. Computer calculation of the sand program, the corresponding fluid program and pumping rates are presented also.

  9. Complex Fluids and Hydraulic Fracturing. (United States)

    Barbati, Alexander C; Desroches, Jean; Robisson, Agathe; McKinley, Gareth H


    Nearly 70 years old, hydraulic fracturing is a core technique for stimulating hydrocarbon production in a majority of oil and gas reservoirs. Complex fluids are implemented in nearly every step of the fracturing process, most significantly to generate and sustain fractures and transport and distribute proppant particles during and following fluid injection. An extremely wide range of complex fluids are used: naturally occurring polysaccharide and synthetic polymer solutions, aqueous physical and chemical gels, organic gels, micellar surfactant solutions, emulsions, and foams. These fluids are loaded over a wide range of concentrations with particles of varying sizes and aspect ratios and are subjected to extreme mechanical and environmental conditions. We describe the settings of hydraulic fracturing (framed by geology), fracturing mechanics and physics, and the critical role that non-Newtonian fluid dynamics and complex fluids play in the hydraulic fracturing process.

  10. [Distal humerus fractures in children]. (United States)

    Schneidmueller, D; Boettger, M; Laurer, H; Gutsfeld, P; Bühren, V


    Fractures of the distal humerus belong to the most common injuries of the upper arm in childhood. Most frequently occurring is the supracondylar fracture of the distal humerus. In these cases and in the second most common epicondylar fractures, the metaphysis is affected and these fractures are therefore extra-articular. They have to be distinguished from articular fractures regarding therapy and prognosis. The growth potential of the distal epiphysis is very limited as is the possibility of spontaneous correction so that major dislocations should not be left uncorrected. Unstable and especially dislocated articular fractures must be anatomically reconstructed employing various osteosynthetic techniques, mostly combined with immobilization. Insufficient reconstruction, growth disturbance and non-union can result in axial deformities, such as cubitus valgus and varus, restriction of motion, pain and nerve palsy.

  11. Pediatric elbow fractures: MRI evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Beltran, J. (Dept. of Radiology, Hospital for Joint Diseases, New York, NY (United States)); Rosenberg, Z.S. (Dept. of Radiology, Hospital for Joint Diseases, New York, NY (United States)); Kawelblum, M. (Dept. of Orthopaedic Surgery, Hospital for Joint Diseases, New York, NY (United States)); Montes, L. (Dept. of Radiology, Beth Israel Medical Center, New York, NY (United States)); Bergman, A.G. (Dept. of Radiology, Stanford Univ., School of Medicine, CA (United States)); Strongwater, A. (Dept. of Orthopaedic Surgery, Hospital for Joint Diseases, New York, NY (United States))


    Magnetic resonance imaging (MRI) was performed in eight patients under the age of 8 years who suffered elbow fractures, to assess possible fracture extension into the distal nonossified epiphysis of the humerus in seven cases and to determine the displacement and location of the radial head in one case. MRI allowed accurate depiction of the fracture line when it extended into the cartilaginous epiphysis. In four cases, MRI findings were confirmed at surgery. In five cases, surgery was obviated because no articular extension of the fracture was seen on MRI (4 cases) or because no displacement was noted (1 case). In one patient, the plain film diagnosis of a Salter type II fracture was changed to Salter type IV on the basis of the MRI findings. It is concluded that MRI might play a role in the preoperative evaluation of pediatric patients presenting with elbow trauma when extension of the fracture cannot be determined with routine radiographic studies. (orig.)

  12. Seismic determination of saturation in fractured reservoirs (United States)

    Brown, R.L.; Wiggins, M.L.; Gupta, A.


    Detecting the saturation of a fractured reservoir using shear waves is possible when the fractures have a geometry that induces a component of movement perpendicular to the fractures. When such geometry is present, vertically traveling shear waves can be used to examine the saturation of the fractured reservoir. Tilted, corrugated, and saw-tooth fracture models are potential examples.

  13. Postpartal sacral fracture without osteoporosis. (United States)

    Rousière, M; Kahan, A; Job-Deslandre, C


    Stress fractures of the sacrum during pregnancy or the postpartum seem uncommon. We report a new case of nontrauma-related postpartal sacral fracture. Only four similar cases have been reported to date. The patient was 36 years of age and her fracture was diagnosed four weeks after her first delivery. Vitamin D levels were low, but there was no osteomalacia. Other standard laboratory tests were normal, as were absorptiometry measurements at the lumbar spine and femur. Rheumatologists should consider sacral fracture in pregnant or nursing patients with buttock pain. Magnetic resonance imaging is the diagnostic investigation of choice.

  14. Classification of subtrochanteric femoral fractures. (United States)

    Loizou, C L; McNamara, I; Ahmed, K; Pryor, G A; Parker, M J


    A review of the literature identified 15 different classification methods for subtrochanteric femoral fractures. Only eight of those classifications defined the area of bone, which constituted a subtrochanteric fracture. The actual length of femur defined as the subtrochanteric zone varied from 3 cm up to the level of the femoral isthmus. There was no agreement between the different classifications regarding the proximal and distal border or for those fractures, which traverse anatomical boundaries. In the various classifications, fractures were subdivided into 2-15 subgroups. The majority of the identified studies were unable to find the classifications useful in either determining treatment or predicting the outcome after treatment. We subdivided subtrochanteric fractures into three types based on the degree of fracture comminution. We examined the inter- and intra-observer agreement of our recommended classification. One orthopaedic consultant, one specialist hip fracture surgeon, two trainee registrar orthopaedic surgeons and one specialty trainee in orthopaedics, on two different occasions, 8 weeks apart, independently classified the radiographs of 20 patients with a subtrochanteric fracture. The mean kappa value for inter- and intra-observer variation was 0.71 and 0.79, respectively, with both showing substantial agreement and, therefore, this simpler classification is recommended. Based on the review of previous classification methods, we also recommend that the subtrochanteric zone be defined as the one in which the fracture line crossing the femur is predominantly within the area of bone extending 5 cm below the lower border of the lesser trochanter.

  15. Tensile deformation and fracture behavior of CuZn5 brass alloy at high temperature

    Energy Technology Data Exchange (ETDEWEB)

    Sharififar, M., E-mail:; Akbari Mousavi, S.A.A., E-mail:


    Alpha brass alloys are widely used for production of rectangular waveguides because of their low bulk resistivity. In this paper, the microstructure, tensile deformation and fracture behavior of CuZn5 brass alloy were investigated. The strain rate sensitivity and its relation to post-uniform deformation in tensile test and correlation between strain hardening exponent (n) and temperature were examined. The results show that strain hardening exponent decreases from 0.5 to 0.4 with increase in test temperature from 250 to 450 °C. Tensile fracture mechanisms of as-extruded CuZn5 brass alloy were studied over a range of temperatures from 300 to 450 °C and range of strain rates from 0.01 to 0.4 1/s by means of scanning electron microscope (SEM) and Atomic Force Microscope (AFM). The results show that different fracture mechanisms operate in different temperature and strain rate ranges. While transgranular dimple fracture is dominant at 300 °C and 0.4 1/s, the dominant fracture mechanism at 450 °C and 0.01 1/s is cleavage facets. Precipitations and grain boundary sliding at high temperature may be the mechanism of ductility drop. Dynamic strain ageing (DSA) did not occur since none of the manifestations of DSA are observed.

  16. Fatigue Performance of Microalloyed High-strength Rebar and Analysis of Fracture Mechanism

    Institute of Scientific and Technical Information of China (English)

    Peng-yan LU; Yu LIU; Hua-jie WU; Gang LIU; Xiang MENG; Yang XU


    Fatigue performance of hot-rolled ribbed-steel bar with the yield strength of 500 MPa (HRB500)was stud-ied with bend-rotating fatigue test at a stress ratio of R=-1 .It is determined by staircase method that its fatigue strength for 107 cycles is 451 MPa,which is higher than that of common carbon structural steel.This should be at-tributed to the fine-grain strengthening resulting from the high content of alloy element V and Thermo-Mechanical Control Process (TMCP).The S-N curve function is also obtained by nonlinear regression with three parameters power function.The fatigue fractures of the specimen were further analyzed with Scanning Electron Microscopy (SEM)and Energy Disperse Spectroscopy (EDS)to study the fracture mechanism.Taking into account microstruc-ture,hardness and cleanliness of the material,it implies that the fatigue fractures of HRB500 rebar all arise from surface substrates in which many brittle inclusions are contained,and that the fatigue crack propagation is principally based on the mechanism of quasi-cleavage fracture,because of the intracrystalline hard spots leading to stress con-centration and thus to the cracks.Moreover,the transient breaking area exhibits microvoid coalescence of ductile fracture due to the existing abundant inclusions.

  17. Bilateral Mandibular Condylar Fractures with Associated External Auditory Canal Fractures and Otorrhagia


    Dang, David


    A rare case of bilateral mandibular condylar fractures associated with bilateral external auditory canal fractures and otorrhagia is reported. The more severe external auditory canal fracture was present on the side of high condylar fracture, and the less severe external auditory canal fracture was ipsilateral to the condylar neck fracture. A mechanism of injury is proposed to account for such findings.

  18. Bilateral Mandibular Condylar Fractures with Associated External Auditory Canal Fractures and Otorrhagia. (United States)

    Dang, David


    A rare case of bilateral mandibular condylar fractures associated with bilateral external auditory canal fractures and otorrhagia is reported. The more severe external auditory canal fracture was present on the side of high condylar fracture, and the less severe external auditory canal fracture was ipsilateral to the condylar neck fracture. A mechanism of injury is proposed to account for such findings.

  19. Fracture network growth for prediction of fracture characteristics and connectivity in tight reservoir rocks

    NARCIS (Netherlands)

    Barnhoorn, A.; Cox, S.F.


    Fracturing experiments on very low-porosity dolomite rocks shows a difference in growth of fracture networks by stress-driven fracturing and fluid-driven fracturing. Stress-driven fracture growth, in the absence of fluid pressure, initially forms fractures randomly throughout the rocks followed by g

  20. Lanthanide-Mediated Dephosphorylation Used for Peptide Cleavage during Solid Phase Peptide Synthesis

    Directory of Open Access Journals (Sweden)

    Byunghee Yoo


    Full Text Available Lanthanide(III ions can accelerate the hydrolysis of phosphomonoesters and phosphodiesters in neutral aqueous solution. In this paper, lanthanide-mediated dephosphorylation has been applied in aqueous media as an orthogonal cleavage condition that can be employed in conventional solid phase peptide synthesis (SPPS. A phosphorylated polymeric support for SPPS was developed using Boc chemistry. The cleavage of resin-bound phosphates was investigated with the addition of Eu(III, Yb(III, acid or base, a mixture of solvents or different temperatures. To demonstrate the utility of this approach for SPPS, a peptide sequence was synthesized on a phosphorylated polymeric support and quantitatively cleaved with lanthanide ions in neutral aqueous media. The protecting groups for side chains were retained during peptide cleavage using lanthanide ions. This new methodology provides a mild orthogonal cleavage condition of phosphoester as a linker during SPPS.

  1. Facile P-C/C-H Bond-Cleavage Reactivity of Nickel Bis(diphosphine) Complexes. (United States)

    Zhang, Shaoguang; Li, Haixia; Appel, Aaron M; Hall, Michael B; Bullock, R Morris


    Unusual cleavage of P-C and C-H bonds of the P2 N2 ligand, in heteroleptic [Ni(P2 N2 )(diphosphine)](2+) complexes under mild conditions, results in the formation of an iminium formyl nickelate featuring a C,P,P-tridentate coordination mode. The structures of both the heteroleptic [Ni(P2 N2 )(diphosphine)](2+) complexes and the resulting iminium formyl nickelate have been characterized by NMR spectroscopy and single-crystal X-ray diffraction analysis. Density functional theory (DFT) calculations were employed to investigate the mechanism of the P-C/C-H bond cleavage, which involves C-H bond cleavage, hydride rotation, Ni-C/P-H bond formation, and P-C bond cleavage.

  2. Photolytic Cleavage and Condensation Reactions of Cyclohexa-2,4-dienones with Diamines

    Directory of Open Access Journals (Sweden)

    Sung Kee Chung


    Full Text Available Cyclohexa-2,4-diene-1-one sulfone derivate undergoes ring cleavage to afford bis-amides containing a diene moiety on irradiation with visible light in the presence of various diamines.

  3. Site-Specific Pyrolysis Induced Cleavage at Aspartic Acid Residue in Peptides and Proteins (United States)

    Zhang, Shaofeng; Basile, Franco


    A simple and site-specific non-enzymatic method based on pyrolysis has been developed to cleave peptides and proteins. Pyrolytic cleavage was found to be specific and rapid as it induced a cleavage at the C-terminal side of aspartic acid in the temperature range of 220–250 °C in 10 seconds. Electrospray Ionization (ESI) mass spectrometry (MS) and tandem-MS (MS/MS) were used to characterize and identify pyrolysis cleavage products, confirming that sequence information is conserved after the pyrolysis process in both peptides and protein tested. This suggests that pyrolysis-induced cleavage at aspartyl residues can be used as a rapid protein digestion procedure for the generation of sequence specific protein biomarkers. PMID:17388620

  4. Biomarkers derived from heterolytic and homolytic cleavage of allylic hydroperoxides resulting from alkenone autoxidation

    Digital Repository Service at National Institute of Oceanography (India)

    Rontania, J.F.; Harji, R.; Volkmanc, J.K.

    , hydroxyacids and alkyldiols resulted from the reduction during the NaBH4 treatment of the corresponding aldehydes, ketoxyacids and ketoxyaldehydes formed from heterolytic or hemolytic cleavages of allylic hydroperoxyl groups resulting from the oxidation...

  5. Fracture Rates and Fracture Sites in Patients With Osteogenesis Imperfecta

    DEFF Research Database (Denmark)

    Folkestad, Lars; Hald, Jannie Dahl; Ersbøll, Annette Kjaer;


    , with a peak during the toddler and adolescent years (incidence rate [IR] 233.9 per 1000 person years), fewer fractures during adulthood (IR 84.5 per 1000 person years), and increased fracture rates in older women (IR 111.9 per 1000 person years). This is the largest register-based nationwide study...... years. In comparison, 709 persons in the reference population experienced a total of 1018 fractures during follow-up. Both male and female patients with OI had an increased fracture rate throughout their life. The fracture rate ratio for participants aged 0 to 19 years was 10.7, for participants aged 20...... to 54 years 17.2, and for participants aged 55 years and over 4.1 when compared to the reference population. The highest fracture rate was seen in males with OI aged 0 to 19 years (257 fractures per 1000 person-years). The fractures appear to follow the same pattern as in the general population...

  6. Modelling of Specimen Fracture (United States)


    the plate center. An end load of 1.0 MPa was applied. 1 2 3 Modelling of Specimen Fracture – Final Report 11 TR-13-47 Figure 2.5: Crack Geometry Figure...Christopher Bayley DRDC Atlantic Dockyard Laboratory Pacific CFB Esquimalt, Building 199 PO Box 17000, Station Forces Victoria, British Columbia Canada...q The weighting function, q , can be any arbitrary function within the J-integral domain, and must be zero on the domain boundary . An easy function

  7. From Bedding To Cleavage: The Evolution Of Clay Fabric Near A Thrust. (United States)

    Boiron, T.; Aubourg, C.; Valier, P., Sr.


    In foothills, the propagation of faults within incompetent bed is potentially accompanied by the development of oblique cleavage. This is particularly demonstrated in the Southern Pyrenees where the out-of-sequence propagation of a flat thrust imposed the development of oblique cleavage within the flat-lying Pamplona marls. Over hundreds of meters, it is possible to trace step by step the cleavage development. The horizontal bedding is gradually superimposed by oblique cleavage (dip ~60°N). At the end of the studied outcrop, a pervasive ~mm spaced cleavage is observed. The anisotropy of magnetic susceptibility (AMS) is a classic tool for study the deformation in shales. In the Pamplona marls, AMS is essentially controlled by clays fabric. AMS shows that the degree of anisotropy Pj is not the best parameter to highlight the degree of deformation of marls. This parameter is positively correlated to the bulk magnetic susceptibility Km (~10-4 SI). On the contrary, the shape parameter T is more consistent with the degree of deformation: higher is the degree of deformation observed in outcrop (occurrence of pervasive cleavage), lower is the T parameter. As m-spaced cleavage starts to develop, the shape parameter T decreases linearly from ~0.8 to ~0.2, reflecting a gradual disorganization of clay particles. Despite the development of mm-spaced cleavage, the magnetic fabric remains oblate and is still dominated by the sedimentary fabric. This means that the bulk fabric of clay particles remains parallel to the bedding plane. Our study demonstrates that AMS is a powerful tool to trace the deformation of clay rocks and that the study of the shape parameter T is a robust and fast gauge of clays fabric. .

  8. Specific detection of the cleavage activity of mycobacterial enzymes using a quantum dot based DNA nanosensor (United States)

    Jepsen, Morten Leth; Harmsen, Charlotte; Godbole, Adwait Anand; Nagaraja, Valakunja; Knudsen, Birgitta R.; Ho, Yi-Ping


    We present a quantum dot based DNA nanosensor specifically targeting the cleavage step in the reaction cycle of the essential DNA-modifying enzyme, mycobacterial topoisomerase I. The design takes advantages of the unique photophysical properties of quantum dots to generate visible fluorescence recovery upon specific cleavage by mycobacterial topoisomerase I. This report, for the first time, demonstrates the possibility to quantify the cleavage activity of the mycobacterial enzyme without the pre-processing sample purification or post-processing signal amplification. The cleavage induced signal response has also proven reliable in biological matrices, such as whole cell extracts prepared from Escherichia coli and human Caco-2 cells. It is expected that the assay may contribute to the clinical diagnostics of bacterial diseases, as well as the evaluation of treatment outcomes.We present a quantum dot based DNA nanosensor specifically targeting the cleavage step in the reaction cycle of the essential DNA-modifying enzyme, mycobacterial topoisomerase I. The design takes advantages of the unique photophysical properties of quantum dots to generate visible fluorescence recovery upon specific cleavage by mycobacterial topoisomerase I. This report, for the first time, demonstrates the possibility to quantify the cleavage activity of the mycobacterial enzyme without the pre-processing sample purification or post-processing signal amplification. The cleavage induced signal response has also proven reliable in biological matrices, such as whole cell extracts prepared from Escherichia coli and human Caco-2 cells. It is expected that the assay may contribute to the clinical diagnostics of bacterial diseases, as well as the evaluation of treatment outcomes. Electronic supplementary information (ESI) available: Characterization of the QD-based DNA Nanosensor. See DOI: 10.1039/c5nr06326d

  9. Cleavage and protection of locked nucleic acid-modified DNA by restriction endonucleases

    DEFF Research Database (Denmark)

    Crouzier, Lucile; Dubois, Camille; Wengel, Jesper;


    Locked nucleic acid (LNA) is one of the most prominent nucleic acid analogues reported so far. We herein for the first time report cleavage by restriction endonuclease of LNA-modified DNA oligonucleotides. The experiments revealed that RsaI is an efficient enzyme capable of recognizing and cleaving...... LNA-modified DNA oligonucleotides. Furthermore, introduction of LNA nucleotides protects against cleavage by the restriction endonucleases PvuII, PstI, SacI, KpnI and EcoRI....

  10. Photocatalytic C-C Bond Cleavage and Amination of Cycloalkanols by Cerium(III) Chloride Complex. (United States)

    Guo, Jing-Jing; Hu, Anhua; Chen, Yilin; Sun, Jianfeng; Tang, Haoming; Zuo, Zhiwei


    A general strategy for the cleavage and amination of C-C bonds of cycloalkanols has been achieved through visible-light-induced photoredox catalysis utilizing a cerium(III) chloride complex. This operationally simple methodology has been successfully applied to a wide array of unstrained cyclic alcohols, and represents the first example of catalytic C-C bond cleavage and functionalization of unstrained secondary cycloalkanols.

  11. A strategy for developing a hammerhead ribozyme for selective RNA cleavage depending on substitutional RNA editing


    Fukuda, Masatora; Kurihara, Kei; Tanaka, Yasuyoshi; Deshimaru, Masanobu


    Engineered site-specific RNA cleavage is widely used for gene regulation, RNA mapping, and synthetic RNA production. Here the authors extend the range of engineered recognition selectivity to include cleavage of sequence motifs containing naturally occurring base modifications. They describe and implement a designer hammerhead ribozyme that cleaves a target sequence 1 nt from a site of adenosine to inosine (A-to-I) or cytosine to uracil (C-to-U) editing in synthetic or physiological mRNA cont...

  12. Control of extracellular cleavage of ProBDNF by high frequency neuronal activity


    Nagappan, Guhan; Zaitsev, Eugene; Senatorov, Vladimir V.; Yang, Jianmin; Hempstead, Barbara L.; Lu, Bai


    Pro- and mature neurotrophins often elicit opposing biological effects. For example, mature brain-derived neurotrophic factor (mBDNF) is critical for long-term potentiation induced by high-frequency stimulation, whereas proBDNF facilitate long-term depression induced by low-frequency stimulation. Because mBDNF is derived from proBDNF by endoproteolytic cleavage, mechanisms regulating the cleavage of proBDNF may control the direction of BDNF regulation. Using methods that selectively detect pr...

  13. Gravity-Driven Hydraulic Fractures (United States)

    Germanovich, L. N.; Garagash, D.; Murdoch, L. C.; Robinowitz, M.


    This study is motived by a new method for disposing of nuclear waste by injecting it as a dense slurry into a hydraulic fracture that grows downward to great enough depth to permanently isolate the waste. Disposing of nuclear waste using gravity-driven hydraulic fractures is mechanically similar to the upward growth of dikes filled with low density magma. A fundamental question in both applications is how the injected fluid controls the propagation dynamics and fracture geometry (depth and breadth) in three dimensions. Analog experiments in gelatin [e.g., Heimpel and Olson, 1994; Taisne and Tait, 2009] show that fracture breadth (the short horizontal dimension) remains nearly stationary when the process in the fracture "head" (where breadth is controlled) is dominated by solid toughness, whereas viscous fluid dissipation is dominant in the fracture tail. We model propagation of the resulting gravity-driven (buoyant or sinking), finger-like fracture of stationary breadth with slowly varying opening along the crack length. The elastic response to fluid loading in a horizontal cross-section is local and can be treated similar to the classical Perkins-Kern-Nordgren (PKN) model of hydraulic fracturing. The propagation condition for a finger-like crack is based on balancing the global energy release rate due to a unit crack extension with the rock fracture toughness. It allows us to relate the net fluid pressure at the tip to the fracture breadth and rock toughness. Unlike the PKN fracture, where breadth is known a priori, the final breadth of a finger-like fracture is a result of processes in the fracture head. Because the head is much more open than the tail, viscous pressure drop in the head can be neglected leading to a 3D analog of Weertman's hydrostatic pulse. This requires relaxing the local elasticity assumption of the PKN model in the fracture head. As a result, we resolve the breadth, and then match the viscosity-dominated tail with the 3-D, toughness

  14. Image diagnosis of nasal bone fracture

    Energy Technology Data Exchange (ETDEWEB)

    Hirota, Yoshiharu; Shimizu, Yayoi; Iinuma, Toshitaka.


    Twenty cases of nasal bone fractures were evaluated as to the types of fractures based upon HRCT findings. Conventional X-Ray films for nasal bones were analyzed and compared with HRCT findings. Nasal bone fractures were classified into lateral and frontal fractures. HRCT images were evaluated in three planes including upper, middle and lower portions of the nasal bone. Fractures favored males of teens. Lateral fracture gave rise to the fractures of the nasal bone opposite to the external force, loosening of the ipsilateral nasomaxillary sutures and fractures of the frontal process of the maxilla. Conventional X-Ray films were reevaluated after HRCT evaluation and indications of nasal bone fractures were determined. In addition to the discontinuity of the nasal dorsum, fracture lines parallel to and beneath the nasal dorsum and indistinct fracture lines along the nasomaxillary sutures are the indication of nasal bone fractures by conventional X-Ray films.

  15. Carbon-carbon bond cleavage in activation of the prodrug nabumetone. (United States)

    Varfaj, Fatbardha; Zulkifli, Siti N A; Park, Hyoung-Goo; Challinor, Victoria L; De Voss, James J; Ortiz de Montellano, Paul R


    Carbon-carbon bond cleavage reactions are catalyzed by, among others, lanosterol 14-demethylase (CYP51), cholesterol side-chain cleavage enzyme (CYP11), sterol 17β-lyase (CYP17), and aromatase (CYP19). Because of the high substrate specificities of these enzymes and the complex nature of their substrates, these reactions have been difficult to characterize. A CYP1A2-catalyzed carbon-carbon bond cleavage reaction is required for conversion of the prodrug nabumetone to its active form, 6-methoxy-2-naphthylacetic acid (6-MNA). Despite worldwide use of nabumetone as an anti-inflammatory agent, the mechanism of its carbon-carbon bond cleavage reaction remains obscure. With the help of authentic synthetic standards, we report here that the reaction involves 3-hydroxylation, carbon-carbon cleavage to the aldehyde, and oxidation of the aldehyde to the acid, all catalyzed by CYP1A2 or, less effectively, by other P450 enzymes. The data indicate that the carbon-carbon bond cleavage is mediated by the ferric peroxo anion rather than the ferryl species in the P450 catalytic cycle. CYP1A2 also catalyzes O-demethylation and alcohol to ketone transformations of nabumetone and its analogs.

  16. Recycling of protein subunits during DNA translocation and cleavage by Type I restriction-modification enzymes. (United States)

    Simons, Michelle; Szczelkun, Mark D


    The Type I restriction-modification enzymes comprise three protein subunits; HsdS and HsdM that form a methyltransferase (MTase) and HsdR that associates with the MTase and catalyses Adenosine-5'-triphosphate (ATP)-dependent DNA translocation and cleavage. Here, we examine whether the MTase and HsdR components can 'turnover' in vitro, i.e. whether they can catalyse translocation and cleavage events on one DNA molecule, dissociate and then re-bind a second DNA molecule. Translocation termination by both EcoKI and EcoR124I leads to HsdR dissociation from linear DNA but not from circular DNA. Following DNA cleavage, the HsdR subunits appear unable to dissociate even though the DNA is linear, suggesting a tight interaction with the cleaved product. The MTases of EcoKI and EcoAI can dissociate from DNA following either translocation or cleavage and can initiate reactions on new DNA molecules as long as free HsdR molecules are available. In contrast, the MTase of EcoR124I does not turnover and additional cleavage of circular DNA is not observed by inclusion of RecBCD, a helicase-nuclease that degrades the linear DNA product resulting from Type I cleavage. Roles for Type I restriction endonuclease subunit dynamics in restriction alleviation in the cell are discussed.

  17. Potential-modulated DNA cleavage by (N-salicylideneglycinato)copper(II) complex. (United States)

    Yang, Zhou-Sheng; Wang, Yan-Ling; Liu, Yun-Chun; Zhao, Guang-Chao


    The interaction of aqua (N-salicylideneglycinato)copper(II) (Cu(salgly)2+) complex with calf thymus DNA has been investigated by cyclic voltammetry. Potential-modulated DNA cleavage in the presence of Cu(salgly)2+ complex was performed at a gold electrode in a thin layer cell. DNA can be efficiently cleaved by electrochemically reducing Cu(salgly)2+ complex to Cu(salgly)+ complex at -0.7 V (vs. Ag/AgCl). When the solution was aerated with a small flow of O2 during electrolysis, the extent of DNA cleavage was dramatically enhanced, and hydroxyl radical scavengers inhibited DNA cleavage. These results suggested that O2 and hydroxyl radical were involved in potential-modulated DNA cleavage reaction. The percentage of DNA cleavage was enhanced as the working potential was shifted to more negative values and the electrolysis time was increased. It was also dependent on the ratio of Cu(salgly)2+ complex to DNA concentration. The cleaved DNA fragments were separated by high performance liquid chromatography (HPLC). The experimental results indicated that the method for potential-modulated DNA cleavage by Cu(salgly)2+ complex was simple and efficient.

  18. Expression and in vitro cleavage activity of anti-caspase-7 hammerhead ribozymes

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang; Qing Xie; Xia-Qiu Zhou; Shan Jiang; You-Xin Jin


    AIM: To prepare hammerhead ribozymes against mouse caspase-7 and identify their cleavage activityin vitro, in order to select a ribozyme with specific cleavage activity against mouse caspase-7 as a potential gene therapy for apoptosis-related diseases.METHODS: Anti-caspase-7 ribozymes targeting sites 333and 394 (named Rz333 and Rz394) were designed by computer software, and their DNA sequences encoding ribozymes were synthesized. Caspase-7 DNA sequence was acquired by RT-PCR. Ribozymes and caspase-7 DNA obtained byin vitro transcription were cloned into pBSKneo U6' and pGEM-T vectors, respectively. The cleavage activity of ribozymes against mouse caspase-7 was identified by cleavage experimentsin vitro.RESULTS: Rz333 and Rz394 were designed and their DNA sequences were synthesized respectively. The expression vector of caspase-7 and plasmids containing Rz333 and Rz394 were reconstructed successfully. Ribozymes and caspase-7 mRNA were expressed byin vitro transcription.In vitro cleavage experiment showed that 243-nt and 744-nt segments were produced after caspase-7 mRNA was mixed with Rz333 in equivalent, and the cleavage efficiency was 67.98%. No cleaved segment was observed when caspase-7 mRNA was mixed with Rz394.CONCLUSION: Rz333 can site-specific cleave mouse caspase-7 mRNA, and it shows a potential for gene therapy of apoptosis-related diseases by down-regulating gene expression of caspase-7.

  19. Glycoprotein B cleavage is important for murid herpesvirus 4 to infect myeloid cells. (United States)

    Glauser, Daniel L; Milho, Ricardo; Frederico, Bruno; May, Janet S; Kratz, Anne-Sophie; Gillet, Laurent; Stevenson, Philip G


    Glycoprotein B (gB) is a conserved herpesvirus virion component implicated in membrane fusion. As with many-but not all-herpesviruses, the gB of murid herpesvirus 4 (MuHV-4) is cleaved into disulfide-linked subunits, apparently by furin. Preventing gB cleavage for some herpesviruses causes minor infection deficits in vitro, but what the cleavage contributes to host colonization has been unclear. To address this, we mutated the furin cleavage site (R-R-K-R) of the MuHV-4 gB. Abolishing gB cleavage did not affect its expression levels, glycosylation, or antigenic conformation. In vitro, mutant viruses entered fibroblasts and epithelial cells normally but had a significant entry deficit in myeloid cells such as macrophages and bone marrow-derived dendritic cells. The deficit in myeloid cells was not due to reduced virion binding or endocytosis, suggesting that gB cleavage promotes infection at a postendocytic entry step, presumably viral membrane fusion. In vivo, viruses lacking gB cleavage showed reduced lytic spread in the lungs. Alveolar epithelial cell infection was normal, but alveolar macrophage infection was significantly reduced. Normal long-term latency in lymphoid tissue was established nonetheless.

  20. Social economy partnerships and the public/private cleavages

    Directory of Open Access Journals (Sweden)

    Joxerramon Bengoetxea


    Full Text Available Public/Private Partnerships can be seen as one particular topos where the divide between the public domain, all levels of the Public Administration and the private initiative and private property is turned into a joint venture rather than a confrontation or a cleavage. Some of the possible combinations of public and private and where public/private partnerships might fit are displayed analytically. The importance of political theory or ideology in conceiving the relationships between ‘public’ and ‘private’, and the conceptions of a market economy as opposed to a social market economy cannot be exaggerated enough, but equally important are the legal or regulatory framework and the underlying dominant legal culture and legal principles, and of course the economic and financial situation. Public/private partnerships thrive in some conditions, but seem to wane in others, and the current predicament is not favourable, taking into account that only the regulatory framework is supportive of these ventures. Los partenariados público-privados se pueden entender como un espacio particular, en el que el sector público, todos los niveles de la administración pública, y la iniciativa privada y la propiedad privada, abordan una empresa conjunta, en lugar mantener posturas contrapuestas. Se muestran algunas de las posibles combinaciones del sector público y privado, en las que tendrían cabida los partenariados público/privados. Es patente la importancia de la teoría o la ideología política para entender las relaciones entre lo público y lo privado, y las concepciones de una economía de mercado frente a una economía social, pero tampoco se puede negar la importancia del marco legal o reglamentario y la cultura jurídica dominante subyacente, y los principios jurídicos, sin olvidar la situación económica y financiera. Los partenariados público-privados prosperan en algunas condiciones, pero no lo hacen siempre, y la situación econ

  1. The role of the methyltransferase domain of bifunctional restriction enzyme RM.BpuSI in cleavage activity.

    Directory of Open Access Journals (Sweden)

    Arthur Sarrade-Loucheur

    Full Text Available Restriction enzyme (REase RM.BpuSI can be described as a Type IIS/C/G REase for its cleavage site outside of the recognition sequence (Type IIS, bifunctional polypeptide possessing both methyltransferase (MTase and endonuclease activities (Type IIC and endonuclease activity stimulated by S-adenosyl-L-methionine (SAM (Type IIG. The stimulatory effect of SAM on cleavage activity presents a major paradox: a co-factor of the MTase activity that renders the substrate unsusceptible to cleavage enhances the cleavage activity. Here we show that the RM.BpuSI MTase activity modifies both cleavage substrate and product only when they are unmethylated. The MTase activity is, however, much lower than that of M1.BpuSI and is thought not to be the major MTase for host DNA protection. SAM and sinefungin (SIN increase the Vmax of the RM.BpuSI cleavage activity with a proportional change in Km, suggesting the presence of an energetically more favorable pathway is taken. We further showed that RM.BpuSI undergoes substantial conformational changes in the presence of Ca(2+, SIN, cleavage substrate and/or product. Distinct conformers are inferred as the pre-cleavage/cleavage state (in the presence of Ca(2+, substrate or both and MTase state (in the presence of SIN and substrate, SIN and product or product alone. Interestingly, RM.BpuSI adopts a unique conformation when only SIN is present. This SIN-bound state is inferred as a branch point for cleavage and MTase activity and an intermediate to an energetically favorable pathway for cleavage, probably through increasing the binding affinity of the substrate to the enzyme under cleavage conditions. Mutation of a SAM-binding residue resulted in altered conformational changes in the presence of substrate or Ca(2+ and eliminated cleavage activity. The present study underscores the role of the MTase domain as facilitator of efficient cleavage activity for RM.BpuSI.

  2. Fracture Detection and Mapping

    Energy Technology Data Exchange (ETDEWEB)

    Goldstein, Norman E.; Iovenitti, Joseph L.


    Because the costs of drilling, completing, and testing a well can be extremely high, it is important to develop better tools and methods for locating high permeability zones prior to drilling, and to develop better tools and methods for identifying and characterizing major fracture zones during the drilling and well testing stages. At the recommendation of the LBL Industry Review Panel on Geothermal Reservoir Technology, we organized and convened a one-day workshop this past July to discuss various aspects of DOE's current and planned activities in fracture detection, to review the geothermal industry's near-term and long-term research needs, to determine the priority of those needs, to disseminate to industry the status of research in progress, and to discuss the possibility of future joint research between industry and DOE. In this paper we present a brief overview of the workshop from the perspective of those who participated in it and provided us with written comments to a questionnaire that was distributed.

  3. Fracture detection and mapping

    Energy Technology Data Exchange (ETDEWEB)

    Goldstein, N.E.; Iovenitti, J.L.


    Because the costs of drilling, completing, and testing a well can be extremely high, it is important to develop better tools and methods for locating high permeability zones prior to drilling, and to develop better tools and methods for identifying and characterizing major fracture zones during the drilling and well testing stages. At the recommendation of the LBL Industry Review Panel on Geothermal Reservoir Technology, we organized and convened a one-day workshop this past July to discuss various aspects of DOE's current and planned activities in fracture detection, to review the geothermal industry's near-term and long-term research needs, to determine the priority of those needs, to disseminate to industry the status of research in progress, and to discuss the possibility of future joint research between industry and DOE. In this paper we present a brief overview of the workshop from the perspective of those who participated in it and provided us with written comments to a questionnaire that was distributed.

  4. Polymer liquids fracture like solids

    DEFF Research Database (Denmark)

    Huang, Qian; Hassager, Ole


    While fracture in brittle solids has been studied for centuries until today, there are few studies on fracture in polymer liquids. Recent developments in experimental techniques, especially the combination of controlled filament stretching rheometry and high speed imaging, have opened new windows...

  5. Epidemiological study on talus fractures

    Directory of Open Access Journals (Sweden)

    Marcos Hideyo Sakaki


    Full Text Available Objective:To analyze the characteristics of patients with talus fractures and the injuries that they present.Methods:Retrospective analysis on patients hospitalized in the Institute of Orthopedics and Traumatology, Hospital das Clínicas, School of Medicine of the University of São Paulo, between 2006 and 2011, with talus fractures. Patient profile parameters, risk factors, fracture characteristics, treatment data and acute complications were analyzed.Results:Analysis on 23 cases showed that men were more affected than women, with a ratio of 4.8:1. The most frequent trauma mechanism was traffic accidents, followed by falls from a height. The most frequent type of fracture was at the neck of the talus, with 17 cases. Among the 23 cases, seven had peritalar dislocation at the time of presentation, four had exposed fractures and 11 presented other associated fractures. The mean length of time between the trauma and the definitive treatment was six days, while the mean length of hospital stay was 11 days. Three patients presented acute postoperative complications.Conclusion:Talus fractures occurred most commonly in the region of the talar neck and most frequently in young males who suffered high-energy trauma. In almost half of the cases, there were other associated fractures. The length of hospital stay was 11 days.

  6. Global Trends in Maxillofacial Fractures


    Lee, Kai


    Background The etiology, demographics, fracture site in facial injury patients have been reported worldwide. However, few studies have attempted to identify changes in maxillofacial fractures over time periods and between countries. The statistics are vastly different due to variations in social, environmental, and cultural factors.

  7. Diplopia and orbital wall fractures

    NARCIS (Netherlands)

    Boffano, P.; Roccia, F.; Gallesio, C.; Karagozoglu, K.H.; Forouzanfar, T.


    Diplopia is a symptom that is frequently associated with orbital wall fractures. The aim of this article was to present the incidence and patterns of diplopia after orbital wall blow-out fractures in 2 European centers, Turin and Amsterdam, and to identify any correlation between this symptom and su

  8. Excess mortality following hip fracture

    DEFF Research Database (Denmark)

    Abrahamsen, B; van Staa, T; Ariely, R;


    Summary This systematic literature review has shown that patients experiencing hip fracture after low-impact trauma are at considerable excess risk for death compared with nonhip fracture/community control populations. The increased mortality risk may persist for several years thereafter, highlig...

  9. Bilateral acetabular fracture without trauma


    De Rosa, M. A.; G. Maccauro; D’Arienzo, M.


     In the absence of trauma fracture of the acetabulum is an extremely rare injury. We describe a 70 year old man who spontaneously developed fractures in both acetabulae due to bony insufficiency. It was successfully treated by bilateral total hip replacement.

  10. Modeling Dynamic Fracture of Cryogenic Pellets

    Energy Technology Data Exchange (ETDEWEB)

    Parks, Paul [General Atomics, San Diego, CA (United States)


    of a rigorously derived profile) we derived the strain energy associated with the deflection and applied a virtual work principle to find a relationship between the impact (load) pressure to the measured wall deflection depth. The inferred impact pressure was in good agreement with the expected pressure for oblique cryogenic pellet impacts where the pellet shear stress causing cleavage fracture is well above the yield stress for pure shear. The section is concluded with additional discussion on how this wall deformation data lends further support to the analytical fracture model presented in Part I. In Part III we present three different size distribution models. A summary, with a few brief suggestions for a follow on study, is provided at the end of this report.

  11. Carbon-Oxygen Bond Cleavage by Bis(imino)pyridine Iron Compounds : Catalyst Deactivation Pathways and Observation of Acyl C-O Bond Cleavage in Esters

    NARCIS (Netherlands)

    Trovitch, Ryan J.; Lobkovsky, Emil; Bouwkamp, Marco W.; Chirik, Paul J.


    Investigations into the substrate scope of bis(imino)pyridine iron-catalyzed hydrogenation and [2 pi + 2 pi]. diene cyclization reactions identified C-O bond cleavage as a principal deactivation pathway. Addition of diallyl or allyl ethyl ether to the bis(imino)pyridine iron dinitrogen complex, ((iP

  12. Isolated Transverse Sacrum Fracture: A Case Report

    Directory of Open Access Journals (Sweden)

    Cemil Kavalci


    Full Text Available Sacral fracture commonly results from high-energy trauma. Most insufficiency fractures of the sacrum are seen in women after the age of 70. Fractures of the sacrum are rare and generally combined with a concomitant pelvic fracture. Transverse sacral fractures are even less frequent which constitute only 3–5% of all sacral fractures. This type of fractures provide a diagnostic challenge. We report a unique case of isolated transverse fracture of sacrum in a young man sustained low-energy trauma. The patient presented to our emergency department after several hours of injury, and diagnosed by clinical features and roentgenogram findings.

  13. Hydraulic fracturing with chlorine dioxide cleanup

    Energy Technology Data Exchange (ETDEWEB)

    Williams, D.A.; Newlove, J.C.; Horton, R.L.


    This patent describes a method for fracturing a subterranean formation penetrated by a wellbore. It comprises: injecting a fracturing fluid into the formation to form a vertical fracture therein, the fracturing fluid being gelled with a polymer selected from guar, guar derivatives, acrylamide, acrylamide derivatives, cellulose, cellulose derivatives, and mixtures thereof and crosslinked with an organometallic crosslinking compound and having temperature stability above about 175{degrees} F.; packing the fracture with particulate propping agent; backflowing fluids from the formation through the propped fracture to remove a portion of the polymer; injecting at matrix rates sufficient aqueous solution of chlorine dioxide down the wellbore and into the propped fracture to penetrate at least 60 feet of the propped fracture length and contact polymer in the fracturing fluid and polymer residue in the propped fracture and on the fracture walls, the amount of the chlorine dioxide in the aqueous medium being sufficient to degrade polymer in the fracturing fluid and polymer residue; permitting the chlorine dioxide to remain in contact with the polymer in the fracturing fluid and with the polymer residue on the fracture walls and in the fracture for sufficient time to degrade the polymer thereby reducing the fracturing fluid viscosity and dissolving portions of the polymer residue; and flowing formation fluid from the formation through the propped fracture and into the wellbore to remove substantial portions of the polymer and degraded polymer from the fracture.

  14. Degradation of impact fracture during accelerated aging of weld metal on microalloyed steel; Degradacion de la tenacidad al impacto durante el envejecimiento acelerado de soldadura en acero microaleado

    Energy Technology Data Exchange (ETDEWEB)

    Vargas-Arista, B.; Hallen, J. M.; Albiter, A.; Angeles-Chavez, C.


    The effect of accelerated aging on the toughness and fracture of the longitudinal weld metal on an API5L-X52 line pipe steel was evaluated by Charpy V-notch impact test, fracture analysis and transmission electron microscopy. Aging was performed at 250 degree centigrade for 100 to 1000 h. The impact results indicated a significant reduction in the fracture energy and impact toughness as a function of aging time, which were achieved by the scanning electron microscope fractography that showed a decrease in the vol fraction of microvoids by Charpy ductile failure with the aging time, which favored the brittle fracture by transgranular cleavage. The minimum vol fraction of microvoids was reached at 500 h due to the peak aged. The microstructural analysis indicated the precipitation of transgranular iron nano carbides in the aged specimens, which was related to the deterioration of toughness and change in the ductile to brittle behavior. (Author) 15 refs.

  15. Collagen turnover after tibial fractures

    DEFF Research Database (Denmark)

    Joerring, S; Krogsgaard, M; Wilbek, H;


    collagen. A group comparison showed characteristic sequential changes in the turnover of types I and III collagen in fractures of the tibial diaphysis and tibial condyles. The turnover of type III collagen reached a maximum after 2 weeks in both groups. The synthesis of type I collagen reached a maximum......Collagen turnover after tibial fractures was examined in 16 patients with fracture of the tibial diaphysis and in 8 patients with fracture in the tibial condyle area by measuring sequential changes in serological markers of turnover of types I and III collagen for up to 26 weeks after fracture....... The markers were the carboxy-terminal extension peptide of type I procollagen (PICP), the amino-terminal extension peptide of type III procollagen (PIIINP), and the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP). The latter is a new serum marker of degradation of type I...

  16. Flexible fixation and fracture healing

    DEFF Research Database (Denmark)

    Schmal, Hagen; Strohm, Peter C; Jaeger, Martin


    , noncomminuted fractures. External fixation uses external bars for stabilization, whereas internal fixation is realized by subcutaneous placement of locking plates. Both of these "biologic" osteosynthesis methods allow a minimally invasive approach and do not compromise fracture hematoma and periosteal blood...... of articular fractures. They allow for subchondral stabilization using small-diameter angular stable screws as well as buttressing of the joint and the metaphyseal component of a fracture. Biomechanically, they can be far stiffer than external fixators, because subcutaneous plates are located much closer...... to the bone surface than external fixator bars. External fixators have the advantage of being less expensive, highly flexible, and technically less demanding. They remain an integral part of orthopaedic surgery for emergent stabilization, for pediatric fractures, for definitive osteosynthesis in certain...

  17. Distal clavicle fractures in children☆ (United States)

    Labronici, Pedro José; da Silva, Ricardo Rodrigues; Franco, Marcos Vinícius Viana; Labronici, Gustavo José; Pires, Robinson Esteves Santos; Franco, José Sergio


    Objective To analyze fractures of the distal clavicle region in pediatric patients. Methods Ten patients between the ages of five to eleven years (mean of 7.3 years) were observed. Nine patients were treated conservatively and one surgically. All the fractures were classified using the Nenopoulos classification system. Results All the fractures consolidated without complications. Conservative treatment was used for nine patients, of whom three were in group IIIB, three IIb, two IIa and one IV. The only patient who was treated surgically was a female patient of eleven years of age with a group IV fracture. Conclusion The treatment indication for distal fractures of the clavicle in children should be based on the patient's age and the displacement of the fragments. PMID:26962489

  18. Pathogenesis of osteoporotic hip fractures. (United States)

    McClung, Michael R


    Osteoporosis is characterized late in the course of the disease by an increased risk of fracture, particularly in the elderly. It occurs in both sexes, affecting approximately 8 million women and 2 million men aged > or = 50 years (1). While low bone density is a predictor of fractures, it is not the only determinant of fracture risk. Other factors include advanced age, altered bone quality, a personal or family history of falls, frailty, poor eyesight, debilitating diseases, and high bone turnover. A diet with sufficient calcium and vitamin D is important to minimize bone loss and, along with regular exercise, to maintain muscle strength. Bisphosphonates have been shown to reduce the risk of hip fracture. For elderly patients, the use of hip protectors may be used as a treatment of last resort. Regardless of the age of the patient, individual patient risk factors must be considered to target appropriate treatment and prevent fracture.

  19. Distal clavicle fractures in children

    Directory of Open Access Journals (Sweden)

    Pedro José Labronici


    Full Text Available ABSTRACT OBJECTIVE: To analyze fractures of the distal clavicle region in pediatric patients. METHODS: Ten patients between the ages of five to eleven years (mean of 7.3 years were observed. Nine patients were treated conservatively and one surgically. All the fractures were classified using the Nenopoulos classification system. RESULTS: All the fractures consolidated without complications. Conservative treatment was used for nine patients, of whom three were in group IIIB, three IIb, two IIa and one IV. The only patient who was treated surgically was a female patient of eleven years of age with a group IV fracture. CONCLUSION: The treatment indication for distal fractures of the clavicle in children should be based on the patient's age and the displacement of the fragments.

  20. Requirements for efficient proteolytic cleavage of prelamin A by ZMPSTE24.

    Directory of Open Access Journals (Sweden)

    Jemima Barrowman

    Full Text Available BACKGROUND: The proteolytic maturation of the nuclear protein lamin A by the zinc metalloprotease ZMPSTE24 is critical for human health. The lamin A precursor, prelamin A, undergoes a multi-step maturation process that includes CAAX processing (farnesylation, proteolysis and carboxylmethylation of the C-terminal CAAX motif, followed by ZMPSTE24-mediated cleavage of the last 15 amino acids, including the modified C-terminus. Failure to cleave the prelamin A "tail", due to mutations in either prelamin A or ZMPSTE24, results in a permanently prenylated form of prelamin A that underlies the premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS and related progeroid disorders. METHODOLOGY/PRINCIPAL FINDINGS: Here we have investigated the features of the prelamin A substrate that are required for efficient cleavage by ZMPSTE24. We find that the C-terminal 41 amino acids of prelamin A contain sufficient context to allow cleavage of the tail by ZMPSTE24. We have identified several mutations in amino acids immediately surrounding the cleavage site (between Y646 and L647 that interfere with efficient cleavage of the prelamin A tail; these mutations include R644C, L648A and N650A, in addition to the previously reported L647R. Our data suggests that 9 of the 15 residues within the cleaved tail that lie immediately upstream of the CAAX motif are not critical for ZMPSTE24-mediated cleavage, as they can be replaced by the 9 amino acid HA epitope. However, duplication of the same 9 amino acids (to increase the distance between the prenyl group and the cleavage site impairs the ability of ZMPSTE24 to cleave prelamin A. CONCLUSIONS/SIGNIFICANCE: Our data reveals amino acid preferences flanking the ZMPSTE24 cleavage site of prelamin A and suggests that spacing from the farnesyl-cysteine to the cleavage site is important for optimal ZMPSTE24 cleavage. These studies begin to elucidate the substrate requirements of an enzyme activity critical to human

  1. Identification of BACE1 cleavage sites in human voltage-gated sodium channel beta 2 subunit

    Directory of Open Access Journals (Sweden)

    Kovacs Dora M


    Full Text Available Abstract Background The voltage-gated sodium channel β2 subunit (Navβ2 is a physiological substrate of BACE1 (β-site APP cleaving enzyme and γ-secretase, two proteolytic enzymes central to Alzheimer's disease pathogenesis. Previously, we have found that the processing of Navβ2 by BACE1 and γ-secretase regulates sodium channel metabolism in neuronal cells. In the current study we identified the BACE1 cleavage sites in human Navβ2. Results We found a major (147-148 L↓M, where ↓ indicates the cleavage site and a minor (144145 L↓Q BACE1 cleavage site in the extracellular domain of human Navβ2 using a cell-free BACE1 cleavage assay followed by mass spectrometry. Next, we introduced two different double mutations into the identified major BACE1 cleavage site in human Navβ2: 147LM/VI and 147LM/AA. Both mutations dramatically decreased the cleavage of human Navβ2 by endogenous BACE1 in cell-free BACE1 cleavage assays. Neither of the two mutations affected subcellular localization of Navβ2 as confirmed by confocal fluorescence microscopy and subcellular fractionation of cholesterol-rich domains. Finally, wildtype and mutated Navβ2 were expressed along BACE1 in B104 rat neuroblastoma cells. In spite of α-secretase still actively cleaving the mutant proteins, Navβ2 cleavage products decreased by ~50% in cells expressing Navβ2 (147LM/VI and ~75% in cells expressing Navβ2 (147LM/AA as compared to cells expressing wildtype Navβ2. Conclusion We identified a major (147-148 L↓M and a minor (144-145 L↓Q BACE1 cleavage site in human Navβ2. Our in vitro and cell-based results clearly show that the 147-148 L↓M is the major BACE1 cleavage site in human Navβ2. These findings expand our understanding of the role of BACE1 in voltage-gated sodium channel metabolism.

  2. The inclusion of weld residual stress in fracture margin assessments of embrittled nuclear reactor pressure vessels

    Energy Technology Data Exchange (ETDEWEB)

    Dickson, T.L.; Bass, B.R.; McAfee, W.J.


    Analyses were performed to determine the impact of weld residual stresses in a reactor pressure vessel (RPV) on (1) the generation of pressure temperature (P-T) curves required for maintaining specified fracture prevention margins during nuclear plant startup and shutdown, and (2) the conditional probability of vessel failure due to pressurized thermal shock (PTS) loading. The through wall residual stress distribution in an axially oriented weld was derived using measurements taken from a shell segment of a canceled RPV and finite element thermal stress analyses. The P-T curve derived from the best estimate load analysis and a t / 8 deep flaw, based on K{sub Ic}, was less limiting than the one derived from the current methodology prescribed in the ASME Boiler and Pressure Vessel Code. The inclusion of the weld residual stresses increased the conditional probability of cleavage fracture due to PTS loading by a factor ranging from 2 to 4.

  3. Effect of dislocation blocking on fracture behavior of Al and {alpha}-Fe: a multiscale study

    Energy Technology Data Exchange (ETDEWEB)

    Noronha, S.J.; Farkas, D


    We use a multiscale approach in which results from atomistic simulations are combined with discrete dislocation (DD) dynamics simulations of crack-tip plasticity. The method is used to study the effects of dislocation blocking on the fracture behavior of {alpha}-iron and aluminum. We studied the effects of blocking for distances ranging from 5 nm to 1 mm and find that the fracture resistance is increased with increasing blocking distance. The atomistic and dislocation dynamics simulations show that the blocking of dislocations causes a net decrease in the shear stress projected on the slip plane, preventing further dislocation emission. Semi-brittle cleavage occurs after a certain number of dislocations are emitted, explicitly demonstrating the embrittling effects of dislocation blocking. This effect can contribute to the brittle behavior observed in some nanocrystalline metals.

  4. Complex multilevel lumbar spine fractures with transverse sacral fracture

    Directory of Open Access Journals (Sweden)

    Kshitij Chaudhary


    Full Text Available We report an unusual and complex case of spinal trauma in a 17-year-old boy who presented with a transverse sacral fracture associated with multiple-level lumbar fractures, paraparesis, and bladder involvement. A two-stage surgery was performed. The lumbar spine fractures were treated with posterior instrumented correction of displacements, followed by anterior instrumentation and fusion. The sacral fracture was left untreated. At 5-year followup, the patient had complete neurological recovery except for the right L5 root function. The long-segment lumbar fusion and the untreated displaced sacral fracture contributed to spinal imbalance, due to which the patient is now able to stand only in a crouched posture. Determining the optimal treatment for the case is presented due to the relative rarity of transverse sacral fracture and paucity of evidence-based treatment approaches. In patients with associated lumbar spine fractures that require extension of instrumentation to the upper lumbar spine, it is critical to restore sacropelvic alignment to achieve spinal balance. Adequate reduction of sacropelvic anatomy can be achieved with iliac screw fixation.

  5. A Rare Entity: Bilateral First Rib Fractures Accompanying Bilateral Scapular Fractures

    Directory of Open Access Journals (Sweden)

    Gultekin Gulbahar


    Full Text Available First rib fractures are scarce due to their well-protected anatomic locations. Bilateral first rib fractures accompanying bilateral scapular fractures are very rare, although they may be together with scapular and clavicular fractures. According to our knowledge, no case of bilateral first rib fractures accompanying bilateral scapular fractures has been reported, so we herein discussed the diagnosis, treatment, and complications of bone fractures due to thoracic trauma in bias of this rare entity.

  6. Definition, classification and treatment of destructive fractures

    Directory of Open Access Journals (Sweden)

    FANG Guo-jun


    Full Text Available 【Abstract】 Destructive injury is defined as a very serious damage both to the bone and the soft tissues. But in clinical practice we found that in some fracture cases, the damage to soft tissues is not as severe as 揹estructive injury?indicates, whereas comminuted fractures still cannot show the severity of bone damage. Therefore we proposed a new term 揹estructive fractures?after combining the definition of destructive injury with typical clinic cases. Destructive fractures refer to the fractures whose osseous tissues are damaged too seriously to be repaired, but soft tissues, nerves and veins are less severely injured and can be repaired. From the year 2001 to 2010, 75 cases of destructive fractures were admitted in our department. According to whether the fractures interlinked with the external environment, together with the fracture sites, they were divided into 6 types: a1 type, closed diaphysis destructive fracture; a2 type, open diaphysis destructive fracture; b1 type, closed joint-involved destructive fracture; b2 type, open joint-involved destructive fracture; c1 type, closed mixed destructive fracture; c2 type, open mixed destructive fracture. Corresponding clinical treatments were conducted for each type.The new classification criterion of destructive fracture is simple and practical and thus can be used as an important guide to make reasonable treatment plans for destructive fractures. Key words: Fracture, bone; Classification; Therapeutics

  7. Coronavirus 3CLpro proteinase cleavage sites: Possible relevance to SARS virus pathology

    Directory of Open Access Journals (Sweden)

    Blom Nikolaj


    Full Text Available Abstract Background Despite the passing of more than a year since the first outbreak of Severe Acute Respiratory Syndrome (SARS, efficient counter-measures are still few and many believe that reappearance of SARS, or a similar disease caused by a coronavirus, is not unlikely. For other virus families like the picornaviruses it is known that pathology is related to proteolytic cleavage of host proteins by viral proteinases. Furthermore, several studies indicate that virus proliferation can be arrested using specific proteinase inhibitors supporting the belief that proteinases are indeed important during infection. Prompted by this, we set out to analyse and predict cleavage by the coronavirus main proteinase using computational methods. Results We retrieved sequence data on seven fully sequenced coronaviruses and identified the main 3CL proteinase cleavage sites in polyproteins using alignments. A neural network was trained to recognise the cleavage sites in the genomes obtaining a sensitivity of 87.0% and a specificity of 99.0%. Several proteins known to be cleaved by other viruses were submitted to prediction as well as proteins suspected relevant in coronavirus pathology. Cleavage sites were predicted in proteins such as the cystic fibrosis transmembrane conductance regulator (CFTR, transcription factors CREB-RP and OCT-1, and components of the ubiquitin pathway. Conclusions Our prediction method NetCorona predicts coronavirus cleavage sites with high specificity and several potential cleavage candidates were identified which might be important to elucidate coronavirus pathology. Furthermore, the method might assist in design of proteinase inhibitors for treatment of SARS and possible future diseases caused by coronaviruses. It is made available for public use at our website:

  8. Topography and Atomic Structure Investigations Of (100 Cleavage Surface of In4Se3 Layered Crystals

    Directory of Open Access Journals (Sweden)

    P.V. Galiy


    Full Text Available The atomic microstructure and crystallography of (100 surfaces of In4Se3 layered crystals obtained by cleavage in situ were studied by the methods of scanning tunneling and atomic force microscopies (STM, AFM and low energy electron diffraction (LEED for reflection. The obtained results indicate the existence of periodic corrugated structures on the cleavage surface. It is shown that (100 In4Se3 cleavage surface is structurally stable and doesn't undergo reconstruction in a wide temperature range of 77-295 K. The anisotropy of thermal expansion along the main crystallography directions in the (100 In4Se3 cleavage plane has been shown. The evaluation of the two-dimensional lattice constant in the cleavage (100 surface plane of orthorhombic In4Se3 layered crystal was done. The calculated values of the lattice constants in consequence of LEED study, such as b  11,475 Å and c  3,734 Å, coincide well with those obtained by the AFM and STM (b  13-14 Å and c  4 Å, and correlate, within the errors limits, with the corresponding values obtained by X-ray diffraction (b  12,308(1 Å and c  4,0810(5 Å. Besides, the obtained results of cleavage surface structure studies show the correctness of filtering application concerning topography images and indicate the adequacy of the model used for calculations of the cleavage (100 surfaces lattice constants of In4Se3 in accordance with the LEED results. The influence of the LEED experimental module structure on the results has been considered.

  9. Early history of scapular fractures. (United States)

    Bartoníček, Jan; Kozánek, Michal; Jupiter, Jesse B


    The first to use the term Scapula was Vesalius (1514-1564) and thus it has remained ever since. Probably the oldest injured scapula, from 250 million years ago, was described by Chinese authors of a skeletal examination of a fossilised remains of a dinosaur Yangchuanosaurus hepingensis. In humans, the oldest known scapular fractures date back to the prehistoric and early historic times. In ancient times, a fracture of acromion was described in the treatises of Hippocrates. Early modern history of the treatment of scapular fractures is closely interlinked with the history of the French surgery. The first to point out the existence of these fractures were Petit, Du Verney and Desault in the 18th century. The first study devoted solely to scapular fractures was published by Traugott Karl August Vogt in 1799. Thomas Callaway published in 1849 an extensive dissertation on injuries to the shoulder girdle, in which he discussed a number of cases known at that time. The first radiograph of a scapular fracture was published by Petty in 1907. Mayo Robson (1884), Lambotte (1913) and Lane (1914) were pioneers in the surgical treatment of these fractures, followed in 1923 by the French surgeons Lenormat, Dujarrier and Basset. The first internal fixation of the glenoid fossa, including a radiograph, was published by Fischer in 1939.

  10. [Fractures of the humerus head]. (United States)

    Jaeger, M; Izadpanah, K; Maier, D; Reising, K; Strohm, P C; Südkamp, N P


    Fractures of the proximal humerus are commonly seen especially in the elderly population. High-energy trauma in young people can be distinguished from low-energy trauma in the elderly resulting from falls of a low height which are typically characterized by osteoporosis. A precise analysis of fractures is essential for a good understanding of the fracture and an individual therapy for which the LEGO-Codman classification provided by Hertel is recommended. Nonsurgical therapy is commonly performed and widely accepted not only for simple fractures. For osteosynthesis angular stable implants became the gold standard but are frequently associated with a high rate of complications some of which can be lowered by an improved surgical technique. Even today varus dislocated fractures are challenging, especially in combination with destruction of the medial column. In those cases where stable osteosynthesis can no longer be achieved arthroplasty is indicated. The clinical results of anatomic fracture arthroplasty are strongly related with correct ingrowth of the tuberosities. Reverse fracture arthroplasty may be considered but indications should be interpreted with caution and preferably used in patients older than 75 years.

  11. Fracture of Fe-3wt.% Si single crystals

    Energy Technology Data Exchange (ETDEWEB)

    Prahl, J. [Czech Technical University in Prague, Department of Materials, Trojanova 13, 120 00 Prague 2 (Czech Republic); Machova, A. [Institute of Thermomechanics, Academy of Sciences of the Czech Republic, Dolejskova 5, 182 00 Prague 8 (Czech Republic); Landa, M. [Institute of Thermomechanics, Academy of Sciences of the Czech Republic, Dolejskova 5, 182 00 Prague 8 (Czech Republic); Hausild, P. [Czech Technical University in Prague, Department of Materials, Trojanova 13, 120 00 Prague 2 (Czech Republic)], E-mail:; Karlik, M. [Czech Technical University in Prague, Department of Materials, Trojanova 13, 120 00 Prague 2 (Czech Republic); Spielmannova, A. [Czech Technical University in Prague, Department of Materials, Trojanova 13, 120 00 Prague 2 (Czech Republic); Clavel, M. [Ecole Centrale Paris, LMSS-Mat, CNRS UMR 8579, Grande Voie des Vignes, 92295 Chatenay-Malabry (France); Haghi-Ashtiani, P. [Ecole Centrale Paris, LMSS-Mat, CNRS UMR 8579, Grande Voie des Vignes, 92295 Chatenay-Malabry (France)


    The ductile to brittle transition in {alpha}-iron was studied on four oriented single crystals of a Fe-3wt.% Si alloy using tensile tests of flat-notched specimens, scanning and transmission electron microscopy. The experimental results are compared with molecular dynamic simulations. Single-edge notched specimens were loaded in tension at room temperature, the crack propagated in a (001) plane and in the [1-bar10] direction. The crosshead speed was changed in the range from 0.1 to 5.0mm/min. Under the lowest loading rate, a plastic zone was formed at the notch tip, faster loading lead to brittle fracture. Fractographic analysis of one specimen ruptured at 1mm/min loading showed flat cleavage facets and tongues formed by the interaction of the principal crack with deformation twins. Besides the tongues, the fracture surface of the second sample ruptured at the same loading rate exhibited signs of plastic deformation. In the first specimen, transmission electron microscopy in the vicinity of the fracture surface confirmed deformation twinning and a very low dislocation density. In the second specimen, deformation twinning was assisted by slip of dislocations in the <111> {l_brace}112{r_brace} slip system. Molecular dynamics simulations confirmed that the crack growth has a more brittle character with increasing loading rates. At a slower loading rate, the crack growth is more difficult since it is impeded by emission of shielding dislocations from the crack tip in the <111> {l_brace}112{r_brace} slip system. Twin formation at the crack front was detected in simulations with edge cracks.

  12. Scapular fractures and concomitant injuries

    Directory of Open Access Journals (Sweden)

    Akaraborworn Osaree


    Full Text Available 【Abstract】 Objective: The association of scapular fractures with other life-threatening injuries including blunt thoracic aortic injury is widely recognized. Few studies have investigated this presumed association. In this study, we investigated the incidence of significant associated injuries with scapular fracture and their outcomes. Methods: A retrospective study was conducted from 2005 to 2009 in a level I trauma center in Thailand. All blunt trauma patients were identified. Patients’ demographics, injury mechanism, associated injuries, Injury Severity Score (ISS, and survival outcomes were recorded. The manage-ment of associated injuries with scapular fracture was reviewed, and the risk factors for mortality were identified. Results: Among the 7 345 trauma patients admitted, scapular fractures occurred in 84 cases (1.1%. The mean age was (37.98±15.21 years. Motorcycle crash was the most fre-quent mechanism of injury, occurring in 51 cases (60.7%. Seventy-four patients (88.1% suffering from scapular frac-tures had associated injuries: 5 (6.0% had significant chest injuries, but none of them had blunt thoracic aortic injury. Two patients (2.4% with scapular fractures died. Factors determining the likelihood of mortality were: (1 ISS>25 (LR=8.5, P<0.05; (2 significant associated chest injury (AIS>3, LR=5.3, P<0.05 and (3 significant associated ab-dominal injury (AIS>3, LR=5.3, P<0.05. Conclusion: A blunt scapular fracture may not accom-pany a blunt thoracic aortic injury but it is strongly related to other injuries like chest injury, extremity injury, head injury, etc. If a scapular fracture is found with a high ISS score, high chest or abdomen AIS score, the patient would have a high risk of mortality. Key words: Aortic rupture; Shoulder fractures; Mul-tiple trauma; Mortality

  13. Fracture Union in Closed Interlocking Nail in Humeral Shaft Fractures

    Directory of Open Access Journals (Sweden)

    Ramji Lal Sahu


    Conclusions: The results of the present study indicates that in the presence of proper indications, reamed antegrade intramedullary interlocked nailing appears to be a method of choice for internal fixation of osteoporotic and pathologic fractures.

  14. Treatment of Unstable Ankle Fractures

    Directory of Open Access Journals (Sweden)

    Yaniel Truffín Rodríguez


    Full Text Available Patients with unstable ankle fractures frequently attend the emergency rooms. It is estimated that there are 122 ankle fractures per 100 000 people a year. Surgical treatment of those that are unstable is inevitable since they can not be corrected in a conservative way. Several surgical procedures for repair of such lesions have been described and all of them constitute important tools for the orthopedic surgeon. Therefore, we conducted a literature review to discuss the current management of unstable ankle fractures based on the analysis of the published literature and the experiences in the Dr. Gustavo Aldereguía Lima University General Hospital of Cienfuegos.

  15. Insufficiency fracture after radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Dong Ryul; Huh, Seung Jae [Dept.of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)


    Insufficiency fracture occurs when normal or physiological stress applied to weakened bone with demineralization and decreased elastic resistance. Recently, many studies reported the development of IF after radiation therapy (RT) in gynecological cancer, prostate cancer, anal cancer and rectal cancer. The RT-induced insufficiency fracture is a common complication during the follow-up using modern imaging studies. The clinical suspicion and knowledge the characteristic imaging patterns of insufficiency fracture is essential to differentiate it from metastatic bone lesions, because it sometimes cause severe pain, and it may be confused with bone metastasis.

  16. Operative strategy of acetabular fractures

    Institute of Scientific and Technical Information of China (English)

    WANG Yan; TANG Pei-fu; HUANG Peng


    Anatomic structure of acetabular fractures are complex and operative exposure and fixation are extremely difficult.For those obviously displaced acetabular fractures, close reduction is doomed to cause deformative healing. Open reduction with internal fixation (ORIF) not only results in anatomic reduction, but also brings complications. No matter which method will be adopted, traumatic arthritis or avascular necrosis of femoral head might occur. In order to treat acetabular fractures more effectively, orthopedic surgeons should be required to fully master the acetabular anatomy, biomechanics, classification and the necessary knowledge for complication prevention.

  17. Genetic Predisposition To Acquire a Polybasic Cleavage Site for Highly Pathogenic Avian Influenza Virus Hemagglutinin (United States)

    Nao, Naganori; Yamagishi, Junya; Miyamoto, Hiroko; Igarashi, Manabu; Manzoor, Rashid; Ohnuma, Aiko; Tsuda, Yoshimi; Furuyama, Wakako; Shigeno, Asako; Kajihara, Masahiro; Kishida, Noriko; Yoshida, Reiko


    ABSTRACT Highly pathogenic avian influenza viruses with H5 and H7 hemagglutinin (HA) subtypes evolve from low-pathogenic precursors through the acquisition of multiple basic amino acid residues at the HA cleavage site. Although this mechanism has been observed to occur naturally only in these HA subtypes, little is known about the genetic basis for the acquisition of the polybasic HA cleavage site. Here we show that consecutive adenine residues and a stem-loop structure, which are frequently found in the viral RNA region encoding amino acids around the cleavage site of low-pathogenic H5 and H7 viruses isolated from waterfowl reservoirs, are important for nucleotide insertions into this RNA region. A reporter assay to detect nontemplated nucleotide insertions and deep-sequencing analysis of viral RNAs revealed that an increased number of adenine residues and enlarged stem-loop structure in the RNA region accelerated the multiple adenine and/or guanine insertions required to create codons for basic amino acids. Interestingly, nucleotide insertions associated with the HA cleavage site motif were not observed principally in the viral RNA of other subtypes tested (H1, H2, H3, and H4). Our findings suggest that the RNA editing-like activity is the key mechanism for nucleotide insertions, providing a clue as to why the acquisition of the polybasic HA cleavage site is restricted to the particular HA subtypes. PMID:28196963

  18. Global identification of target recognition and cleavage by the Microprocessor in human ES cells. (United States)

    Seong, Youngmo; Lim, Do-Hwan; Kim, Augustine; Seo, Jae Hong; Lee, Young Sik; Song, Hoseok; Kwon, Young-Soo


    The Microprocessor plays an essential role in canonical miRNA biogenesis by facilitating cleavage of stem-loop structures in primary transcripts to yield pre-miRNAs. Although miRNA biogenesis has been extensively studied through biochemical and molecular genetic approaches, it has yet to be addressed to what extent the current miRNA biogenesis models hold true in intact cells. To address the issues of in vivo recognition and cleavage by the Microprocessor, we investigate RNAs that are associated with DGCR8 and Drosha by using immunoprecipitation coupled with next-generation sequencing. Here, we present global protein-RNA interactions with unprecedented sensitivity and specificity. Our data indicate that precursors of canonical miRNAs and miRNA-like hairpins are the major substrates of the Microprocessor. As a result of specific enrichment of nascent cleavage products, we are able to pinpoint the Microprocessor-mediated cleavage sites per se at single-nucleotide resolution. Unexpectedly, a 2-nt 3' overhang invariably exists at the ends of cleaved bases instead of nascent pre-miRNAs. Besides canonical miRNA precursors, we find that two novel miRNA-like structures embedded in mRNAs are cleaved to yield pre-miRNA-like hairpins, uncoupled from miRNA maturation. Our data provide a framework for in vivo Microprocessor-mediated cleavage and a foundation for experimental and computational studies on miRNA biogenesis in living cells.

  19. Characteristics of the fast electron emission produced during the cleavage of crystals

    Indian Academy of Sciences (India)

    B P Chandra; N L Patel; S S Rahangdale; R P Patel; V K Patle


    The present paper reports the fast electron emission produced during the cleavage of alkali halide crystals and models the dynamics of the process. The mechano-emission arises as a result of the ionization of surface traps at the expense of the energy which is released in the annihilation of the defects which are formed during cleavage. The slow electrons which appear upon the ionization of surface traps are subsequently accelerated in the field of negatively charged segment of the freshly cleaved surface. Considering the basic mechanism of fast electron emission, expressions are derived which are able to explain satisfactorily the temporal, thermal, charge, surface, coloration, water adsorption and other characteristics of the fast electron emission produced during the cleavage of crystals. The decay time of the charges on the newly created surfaces, and the velocity of cracks can be determined from the measurements of fast electron emission produced during the cleavage of crystals. It is shown that two types of diffusing centres are responsible for the charge relaxation and thereby for the emission of fast electrons produced during the cleavage of alkali halide crystals.

  20. Caspase cleavage sites in the human proteome: CaspDB, a database of predicted substrates.

    Directory of Open Access Journals (Sweden)

    Sonu Kumar

    Full Text Available Caspases are enzymes belonging to a conserved family of cysteine-dependent aspartic-specific proteases that are involved in vital cellular processes and play a prominent role in apoptosis and inflammation. Determining all relevant protein substrates of caspases remains a challenging task. Over 1500 caspase substrates have been discovered in the human proteome according to published data and new substrates are discovered on a daily basis. To aid the discovery process we developed a caspase cleavage prediction method using the recently published curated MerCASBA database of experimentally determined caspase substrates and a Random Forest classification method. On both internal and external test sets, the ranking of predicted cleavage positions is superior to all previously developed prediction methods. The in silico predicted caspase cleavage positions in human proteins are available from a relational database: CaspDB. Our database provides information about potential cleavage sites in a verified set of all human proteins collected in Uniprot and their orthologs, allowing for tracing of cleavage motif conservation. It also provides information about the positions of disease-annotated single nucleotide polymorphisms, and posttranslational modifications that may modulate the caspase cleaving efficiency.

  1. Two-step cleavage of hairpin RNA with 5' overhangs by human DICER

    Directory of Open Access Journals (Sweden)

    Suzuki Harukazu


    Full Text Available Abstract Background DICER is an RNase III family endoribonuclease that processes precursor microRNAs (pre-miRNAs and long double-stranded RNAs, generating microRNA (miRNA duplexes and short interfering RNA duplexes with 20~23 nucleotides (nts in length. The typical form of pre-miRNA processed by the Drosha protein is a hairpin RNA with 2-nt 3' overhangs. On the other hand, production of mature miRNA from an endogenous hairpin RNA with 5' overhangs has also been reported, although the mechanism for this process is unknown. Results In this study, we show that human recombinant DICER protein (rDICER processes a hairpin RNA with 5' overhangs in vitro and generates an intermediate duplex with a 29 nt-5' strand and a 23 nt-3' strand, which was eventually cleaved into a canonical miRNA duplex via a two-step cleavage. The previously identified endogenous pre-miRNA with 5' overhangs, pre-mmu-mir-1982 RNA, is also determined to be a substrate of rDICER through the same two-step cleavage. Conclusions The two-step cleavage of a hairpin RNA with 5' overhangs shows that DICER releases double-stranded RNAs after the first cleavage and binds them again in the inverse direction for a second cleavage. These findings have implications for how DICER may be able to interact with or process differing precursor structures.

  2. Distinct mechanisms for DNA cleavage by myoglobin with a designed heme active center. (United States)

    Zhao, Yuan; Du, Ke-Jie; Gao, Shu-Qin; He, Bo; Wen, Ge-Bo; Tan, Xiangshi; Lin, Ying-Wu


    Heme proteins perform diverse biological functions, of which myoglobin (Mb) is a representative protein. In this study, the O2 carrier Mb was shown to cleave double stranded DNA upon aerobic dithiothreitol-induced reduction, which is fine-tuned by an additional distal histidine, His29 or His43, engineered in the heme active center. Spectroscopic (UV-vis and EPR) and inhibition studies suggested that free radicals including singlet oxygen and hydroxyl radical are responsible for efficient DNA cleavage via an oxidative cleavage mechanism. On the other hand, L29E Mb, with a distinct heme active center involving three water molecules in the met form, was found to exhibit an excellent DNA cleavage activity that was not depending on O2. Inhibition and ligation studies demonstrated for the first time that L29E Mb cleaves double stranded DNA into both the nicked circular and linear forms via a hydrolytic cleavage mechanism, which resembles native endonucleases. This study provides valuable insights into the distinct mechanisms for DNA cleavage by heme proteins, and lays down a base for creating artificial DNA endonucleases by rational design of heme proteins. Moreover, this study suggests that the diverse functions of heme proteins can be fine-tuned by rational design of the heme active center with a hydrogen-bonding network.

  3. Prediction of Ductile Fracture Surface Roughness Scaling

    DEFF Research Database (Denmark)

    Needleman, Alan; Tvergaard, Viggo; Bouchaud, Elisabeth


    Experimental observations have shown that the roughness of fracture surfaces exhibit certain characteristic scaling properties. Here, calculations are carried out to explore the extent to which a ductile damage/fracture constitutive relation can be used to model fracture surface roughness scaling....... The scaling properties of the predicted thickness average fracture surfaces are calculated and the results are discussed in light of experimental observations....

  4. Atypical fractures on long term bisphosphonates therapy.

    LENUS (Irish Health Repository)

    Hussein, W


    Bisphosphonates reduce fractures risk in patients with osteoporosis. A new pattern of fractures is now being noted in patients on prolonged bisphosphonate therapy. We report a case of an atypical femoral fracture with preceding pain and highlight the characteristics of these fractures.

  5. Coupled Fracture and Flow in Shale in Hydraulic Fracturing (United States)

    Carey, J. W.; Mori, H.; Viswanathan, H.


    Production of hydrocarbon from shale requires creation and maintenance of fracture permeability in an otherwise impermeable shale matrix. In this study, we use a combination of triaxial coreflood experiments and x-ray tomography characterization to investigate the fracture-permeability behavior of Utica shale at in situ reservoir conditions (25-50 oC and 35-120 bars). Initially impermeable shale core was placed between flat anvils (compression) or between split anvils (pure shear) and loaded until failure in the triaxial device. Permeability was monitored continuously during this process. Significant deformation (>1%) was required to generate a transmissive fracture system. Permeability generally peaked at the point of a distinct failure event and then dropped by a factor of 2-6 when the system returned to hydrostatic failure. Permeability was very small in compression experiments (conformed to Forscheimer's law. The coupled deformation and flow behavior of Utica shale, particularly the large deformation required to initiate flow, indicates the probable importance of activation of existing fractures in hydraulic fracturing and that these fractures can have adequate permeability for the production of hydrocarbon.

  6. Transverse posterior element fractures associated with torsion

    Energy Technology Data Exchange (ETDEWEB)

    Abel, M.S.


    Six examples of a previously undescribed class of transverse vertebral element fractures are presented. These fractures differ from Chance and Smith fractures and their variants in the following respects: (1) the etiology is torsion and not flexion; (2) there is neither distraction of posterior ring fragments nor posterior ligament tears; (3) in contrast to Chance and Smith fractures, extension of the fracture into the vertebral body is absent or minimal; (4) the transverse process of the lumbar vertebra is avulsed at its base with a vertical fracture, not split horizontally. These fractures occur in cervical, lumbar, and sacral vertebrae in normal or compromised areas of the spine.

  7. Fractura bronquial BRONCHIAL FRACTURE

    Directory of Open Access Journals (Sweden)



    Full Text Available El traumatismo torácico es una entidad patológica emergente, relacionada con accidentes automovilísticos. La lesión más frecuente es la fractura costal. Dependiendo de su gravedad, éste puede provocar tórax volante, contusión cardíaca, lesiones vasculares u otras alteraciones. La ruptura bronquial se observa ocasionalmente en traumatismos torácicos cerrados, y por lo general tiene lugar en el tronco principal del árbol tráqueo-bronquial. Su diagnóstico y manejo inicial representan un problema mayor. Los signos clásicos son la persistencia de neumotórax y flujo masivo de aire a través del drenaje torácico; sin embargo también hay casos que no son típicos. Es difícil determinar el momento correcto para iniciar la ventilación mecánica con presión positiva, la que puede aumentar gravemente el flujo de aire a través de la ruptura bronquial y acentuar el neumotórax a tensión. Presentamos el caso de un hombre de 25 años con un traumatismo torácico cerrado, causado por un accidente de automóvil, en quien la broncoscopía demostró una fractura del bronquio lobar medio. Comprobamos en este paciente, que la fibrobroncoscopía es el procedimiento más útil tanto en el diagnóstico, como en el tratamiento inicial y en el seguimiento post operatorio de su fractura bronquiaThoracic trauma is an emerging pathology related to the increase of motor vehicle accidents. Rib fracture is the most frequent injury; depending on the severity of the event it may be associated with flail chest, cardiac contusion, vascular lesions and other injuries. Bronchial rupture is occasionally seen in blunt trauma and it occurs mostly in the main stem of the tracheobronchial tree. It represents a great task in diagnosis and initial management. Persistent pneumothorax and massive airflow by the thoracic drain are the classic signs, however other cases are not so typical. The right moment to begin positive pressure ventilation is challenging, because in

  8. Compression fractures of the back (United States)

    Taking steps to prevent and treat osteoporosis is the most effective way to prevent compression or insufficiency fractures. Getting regular load-bearing exercise (such as walking) can help you avoid bone loss.

  9. The treatment of subtrochanteric fractures

    Directory of Open Access Journals (Sweden)

    Vučetić Čedomir S.


    Full Text Available Subtrochanteric fractures of the femur have a special place because of a significant number of complications following treatment. Powerful loading forces asymmetrically acting to this bone segment, as well as poor vascularization interfere with bone union. There are basically two current approaches in the fixation of subtrochanteric fractures; the first involves a plate with a compression screw and another one is intramedullary (IM nail, with two options: centromedullary (standard interlocking femoral nail and cephalomedullary femoral nail with two modifications, reconstructive and trochanteric. All IM nails may be used by open technique or closed minimal invasive method. IM nailing is favoured in view of a shorter operative time, shorter hospitalisation and complications. Indirect fracture reduction and knowledge of biology of bone fracture may result in full success without any bone graft.

  10. Ankle Fractures Often Not Diagnosed (United States)

    ... injuries. Telltale signs of a fracture include bruising, blisters, significant swelling or bone protruding through the skin. ... for stability. She also advises buying from small shoe stores that have certified orthotists who work with ...

  11. Principles of Hand Fracture Management (United States)

    Haughton, DN; Jordan, D; Malahias, M; Hindocha, S; Khan, W


    The hand is essential in humans for physical manipulation of their surrounding environment. Allowing the ability to grasp, and differentiated from other animals by an opposing thumb, the main functions include both fine and gross motor skills as well as being a key tool for sensing and understanding the immediate surroundings of their owner. Hand fractures are the most common fractures presenting at both accident and emergency and within orthopaedic clinics. Appropriate evaluation at first presentation, as well as during their management, can significantly prevent both morbidity and disability to a patient. These decisions are dependant on a wide range of factors including age, hand dominance, occupation and co-morbidities. A fracture is best described as a soft tissue injury with an associated bony injury. Despite this being the case, this paper intends to deal mainly with the bone injury and aims to discuss both the timing, as well as the methods available, of hand fracture management. PMID:22423303

  12. Fracture risk assessed by Fracture Risk Assessment Tool (FRAX) compared with fracture risk derived from population fracture rates

    DEFF Research Database (Denmark)

    Rubin, Katrine Hass; Abrahamsen, Bo; Hermann, Anne Pernille


    Purpose: To evaluate the performance of the Swedish version of Fracture Risk Assessment Tool (FRAX)) without bone mass density (BMD) in a Danish population to examine the possibility of applying this version to Danish women. METHODS: From the Danish National Register of social security numbers, we...... randomly selected 5000 women living in the region of Southern Denmark aged 40-90 years to receive a mailed questionnaire concerning risk factors for osteoporosis based on FRAX. The predicted 10-year probability of hip fractures was calculated for each woman returning a complete questionnaire using...... the Swedish version of FRAX. The observed 10-year hip fracture risk was also calculated for each woman using age-specific hip fracture rates from the National Hospital Discharge Register and National survival tables. RESULTS: A total of 4194 (84%) women responded to the questionnaire and 3636 (73%) gave...

  13. Mode I fracture toughness of coal

    Energy Technology Data Exchange (ETDEWEB)

    Bhagat, R.B.


    This investigation was undertaken to determine the fracture toughness and tensile strength of coal and to correlate these with the grindability of the coals in order to understand the fracture mechanics behaviour of coal. Results showed statistical relationships for the dependence of fracture toughness on the tensile strength of coal and between the fracture toughness and the Hardgrove Grindability Index. Softer coals have a lower fracture toughness value as coal is a brittle material. 16 references.

  14. New C2 synchondrosal fracture classification system

    Energy Technology Data Exchange (ETDEWEB)

    Rusin, Jerome A.; Ruess, Lynne [Department of Radiology, Nationwide Children' s Hospital, Columbus, OH (United States); The Ohio State University College of Medicine and Public Health, Columbus, OH (United States); Daulton, Robert S. [Department of Radiology, Nationwide Children' s Hospital, Columbus, OH (United States)


    Excessive cervical flexion-extension accompanying mild to severe impact injuries can lead to C2 synchondrosal fractures in young children. To characterize and classify C2 synchondrosal fracture patterns. We retrospectively reviewed imaging and medical records of children who were treated for cervical spine fractures at our institution between 1995 and 2014. We reviewed all fractures involving the five central C2 synchondroses with regard to patient demographics, mechanism of injury, fracture pattern, associated fractures and other injuries, treatment plans and outcome. Fourteen children had fractures involving the central C2 synchondroses. There were nine boys and five girls, all younger than 6 years. We found four distinct fracture patterns. Eleven complete fractures were further divided into four subtypes (a, b, c and d) based on degree of anterior displacement of the odontoid segment and presence of distraction. Nine of these 11 children had fractures through both odontoneural synchondroses and the odontocentral synchondrosis; one had fractures involving both neurocentral synchondroses and the odontoneural synchondrosis; one had fractures through bilateral odontoneural and bilateral neurocentral synchondroses. Three children had incomplete fractures, defined as a fracture through a single odontoneural synchondrosis with or without partial extension into either the odontocentral or the adjacent neurocentral synchondroses. All complete fractures were displaced or angulated. Four had associated spinal cord injury, including two contusions (subtype c fractures) and two fatal transections (subtype d fractures). Most children were treated with primary halo stabilization. Subtype c fractures required surgical fixation. We describe four patterns of central C2 synchondrosal fractures, including two unique patterns that have not been reported. We propose a classification system to distinguish these fractures and aid in treatment planning. (orig.)

  15. Analysis of the competition between brittle and ductile fracture: application for the mechanical behaviour of C-Mn and theirs welds; Etude de la competition dechirure ductile/rupture fragile: application de la tenue mecanique des tubes en acier C-Mn et de leurs joints soudes

    Energy Technology Data Exchange (ETDEWEB)

    Le Corre, V


    This study deals with the fracture behaviour of welded thin structures in the ductile to brittle transition range. It aims to propose a criterion to define the conditions for which the risk of fracture by cleavage does not exist on a cracked structure. The literature review shows that the difficulties of prediction of the fracture behaviour of a structure are related to the dependence of the fracture probability to the mechanical fields at the crack tip. The ductile to brittle transition range thus depends on the studied geometry of the structure. A threshold stress, below which cleavage cannot take place, is defined using fracture tests on notched specimens broken at very low temperature. The finite element numerical simulation of fracture tests onspecimens in the transition range shows a linear relationship between the fracture probability and the volume exceeding the threshold stress, thus showing the relevance of the proposed criterion. Moreover, several relations are established allowing to simplify the identification of the criterion parameters. The criterion is applied to a nuclear structural C-Mn steel, by focusing more particularly on the higher boundary of the transition range. A fracture test on a full-scale pipe is designed, developed, carried out and analysed using its numerical simulation. The results show firstly that, on the structure, the transition range is shifted in temperature, compared to laboratory specimens, due to the low plasticity constraint achieved in thin structures, and secondly that the threshold stress criterion allows to estimate simply this shift. (author)

  16. IRE1α nucleotide sequence cleavage specificity in the unfolded protein response. (United States)

    Poothong, Juthakorn; Sopha, Pattarawut; Kaufman, Randal J; Tirasophon, Witoon


    Inositol-requiring enzyme 1 (IRE1) is a conserved sensor of the unfolded protein response that has protein kinase and endoribonuclease (RNase) enzymatic activities and thereby initiates HAC1/XBP1 splicing. Previous studies demonstrated that human IRE1α (hIRE1α) does not cleave Saccharomyces cerevisiae HAC1 mRNA. Using an in vitro cleavage assay, we show that adenine to cytosine nucleotide substitution at the +1 position in the 3' splice site of HAC1 RNA is required for specific cleavage by hIRE1α. A similar restricted nucleotide specificity in the RNA substrate was observed for XBP1 splicing in vivo. Together these findings underscore the essential role of cytosine nucleotide at +1 in the 3' splice site for determining cleavage specificity of hIRE1α.

  17. Alkene cleavage catalysed by heme and nonheme enzymes: reaction mechanisms and biocatalytic applications. (United States)

    Mutti, Francesco G


    The oxidative cleavage of alkenes is classically performed by chemical methods, although they display several drawbacks. Ozonolysis requires harsh conditions (-78°C, for a safe process) and reducing reagents in a molar amount, whereas the use of poisonous heavy metals such as Cr, Os, or Ru as catalysts is additionally plagued by low yield and selectivity. Conversely, heme and nonheme enzymes can catalyse the oxidative alkene cleavage at ambient temperature and atmospheric pressure in an aqueous buffer, showing excellent chemo- and regioselectivities in certain cases. This paper focuses on the alkene cleavage catalysed by iron cofactor-dependent enzymes encompassing the reaction mechanisms (in case where it is known) and the application of these enzymes in biocatalysis.

  18. Multiple-turnover cleavage of double-stranded DNA by sandwiched zinc-finger nuclease. (United States)

    Mineta, Yusuke; Okamoto, Tomoyuki; Takenaka, Kosuke; Doi, Norio; Aoyama, Yasuhiro; Sera, Takashi


    To refine zinc-finger nuclease (ZFN) technology, we constructed a sandwiched ZFN, in which a DNA cleavage enzyme was sandwiched with two artificial zinc-finger proteins (AZPs). Because the sandwiched ZFN is designed to cleave the DNA between the two AZP-binding sites, the sandwiched ZFN is expected to bind preferentially to a DNA substrate rather than to cleavage products and thereby cleave it with multiple turnovers. To prove the concept, we sandwiched a staphylococcal nuclease (SNase), which cleaves DNA as a monomer, between two 3-finger AZPs. The AZP-sandwiched SNase cleaved large amounts of dsDNA site-specifically. Such multiple-turnover cleavage was not observed with control nucleases that possess a single AZP.

  19. Cleavage-induced termination in U2 snRNA gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Nabavi, Sadeq [Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada N1G 2W1 (Canada); Nazar, Ross N., E-mail: [Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada N1G 2W1 (Canada)


    The maturation of many small nuclear RNAs is dependent on RNase III-like endonuclease mediated cleavage, which generates a loading site for the exosome complex that trims the precursor at its 3' end. Using a temperature sensitive Pac1 nuclease, here we show that the endonuclease cleavage is equally important in terminating the transcription of the U2 snRNA in Schizosaccharomyces pombe. Using a temperature sensitive Dhp1p 5' {yields} 3' exonuclease, we demonstrate that it also is an essential component of the termination pathway. Taken together the results support a 'reversed torpedoes' model for the termination and maturation of the U2 snRNA; the Pac1 endonuclease cleavage provides entry sites for the 3' and 5' exonuclease activities, leading to RNA maturation in one direction and transcript termination in the other.

  20. Scandium(iii) triflate-promoted serine/threonine-selective peptide bond cleavage. (United States)

    Ni, Jizhi; Sohma, Youhei; Kanai, Motomu


    The site-selective cleavage of peptide bonds is an important chemical modification that is useful not only for the structural determination of peptides, but also as an artificial modulator of peptide/protein function and properties. Here we report site-selective hydrolysis of peptide bonds at the Ser and Thr positions with a high conversion yield. This chemical cleavage relies on Sc(iii)-promoted N,O-acyl rearrangement and subsequent hydrolysis. The method is applicable to a broad scope of polypeptides with various functional groups, including a post-translationally modified peptide that is unsuitable for enzymatic hydrolysis. The system was further extended to site-selective cleavage of a native protein, Aβ1-42, which is closely related to the onset of Alzheimer's disease.

  1. Indirect DNA Sequence Recognition and Its Impact on Nuclease Cleavage Activity. (United States)

    Lambert, Abigail R; Hallinan, Jazmine P; Shen, Betty W; Chik, Jennifer K; Bolduc, Jill M; Kulshina, Nadia; Robins, Lori I; Kaiser, Brett K; Jarjour, Jordan; Havens, Kyle; Scharenberg, Andrew M; Stoddard, Barry L


    LAGLIDADG meganucleases are DNA cleaving enzymes used for genome engineering. While their cleavage specificity can be altered using several protein engineering and selection strategies, their overall targetability is limited by highly specific indirect recognition of the central four base pairs within their recognition sites. In order to examine the physical basis of indirect sequence recognition and to expand the number of such nucleases available for genome engineering, we have determined the target sites, DNA-bound structures, and central four cleavage fidelities of nine related enzymes. Subsequent crystallographic analyses of a meganuclease bound to two noncleavable target sites, each containing a single inactivating base pair substitution at its center, indicates that a localized slip of the mutated base pair causes a small change in the DNA backbone conformation that results in a loss of metal occupancy at one binding site, eliminating cleavage activity.

  2. Intergranular fracture in nanocrystalline metals (United States)

    Farkas, D.; van Swygenhoven, H.; Derlet, P. M.


    Crack propagation studies in nanocrystalline Ni samples with mean grain sizes ranging from 5 to 12 nm are reported using atomistic simulations. For all grain sizes pure intergranular fracture is observed. Intergranular fracture is shown to proceed by the coalescence of microvoids formed at the grain boundaries ahead of the crack. The energy released during propagation is higher than the Griffith value, indicating an additional grain-boundary accommodation mechanism.

  3. [Scaphoid fracture in motocross riders]. (United States)

    Knobloch, K; Krämer, R; Redeker, J; Spies, M; Vogt, P M


    Motocross racing is a demanding motorcycling discipline with significant physiological and psychological demands. Upper extremity injuries are frequently encountered. Interestingly, motocross riders present with a significantly stronger left arm, even if the left hand is not dominant. This difference is attributed to the use of the clutch lever with the left hand, which is more frequent in motocross than in Enduro or desert rally. The wrist has been reported to be involved especially among motocross racers in contrast to road racing. Besides wrist fractures, scaphoid fractures have been previously without a detailed analysis of the injury mechanism. We report on three patients suffering scaphoid fractures caused by extreme hyperextension of the wrist during landing after a motocross jump. Two patients presented late three months following the initial trauma (both Herbert type C fractures), while one motocross athlete with a B 2-type scaphoid fracture was admitted to wrist surgery within a week. The B 2-type fracture was treated with open reduction and Herbert-screw fixation, while the C-type fractures were treated by Herbert-screw fixation in addition to a cortico-cancellous bone graft. Within ten weeks after the surgery the patients were back in sport at their given preoperative level. Hyperextension rather than wrist flexion appears as the predominant mechanism of wrist injuries in motocross riders. A more axial impact on the wrist is more likely to produce a radial fracture during the landing phase. Preventive strategies are internal muscular wrist stabilisation using eccentric training and external stabilisation by rigid gloves allowing only limited hyperextension.

  4. Scapular fractures and concomitant injuries

    Institute of Scientific and Technical Information of China (English)

    Osaree Akaraborworn; Burapat Sangthong; Komet Thongkhao; Prattana Chiniramol; Khanitta Kaewsaengrueang


    Objective: The association of scapular fractures with other life-threatening injuries including blunt thoracic aortic injury is widely recognized.Few studies have investigated this presumed association.In this study,wc investigated the incidence of significant associated injuries with scapular fracture and their outcomes.Methods: A retrospective study was conducted from 2005 to 2009 in a level I trauma center in Thailand.All blunt trauma patients were identified.Patients' demographics,injury mechanism,associated injuries,Injury Severity Score (ISS),and survival outcomes were recorded.The management of associated injuries with scapular fracture was reviewed,and the risk factors for mortality were identified.Results: Among the 7 345 trauma patients admitted,scapular fractures occurred in 84 cases (1.1%).The mean age was (37.98±15.21) years.Motorcycle crash was the most frequent mechanism of injury,occurring in 51 cases (60.7%).Seventy-four patients (88.1%) suffering from scapular fractures had associated injuries:5 (6.0%) had significant chest injuries,but none of them had blunt thoracic aortic injury.Two patients (2.4%) with scapular fractures died.Factors determining the likelihood of mortality were:(1) ISS>25(LR=8.5,P<0.05); (2) significant associated chest injury (AIS>3,LR=5.3,P<0.05) and (3) significant associated abdominal injury (AIS>3,LR=5.3,P<0.05).Conclusion: A blunt scapular fracture may not accompany a blunt thoracic aortic injury but it is strongly related to other injuries like chest injury,extremity injury,head injury,etc.If a scapular fracture is found with a high ISS score,high chest or abdomen AIS score,the patient would have a high risk of mortality.

  5. The Nature of the Tensile Fracture in Austempered Ductile Iron with Dual Matrix Microstructure (United States)

    Kilicli, Volkan; Erdogan, Mehmet


    The tensile fracture characteristics of austempered ductile irons with dual matrix structures and different ausferrite volume fractions have been studied for an unalloyed ductile cast iron containing (in wt.%) 3.50 C, 2.63 Si, 0.318 Mn, and 0.047 Mg. Specimens were intercritically austenitized (partially austenitized) in two phase region (α + γ) at various temperatures for 20 min and then quenched into a salt bath held at austempering temperature of 365 °C for various times and then air cooled to room temperature to obtain various ausferrite volume fractions. Conventionally austempered specimens with fully ausferritic matrix and unalloyed as-cast specimens having fully ferritic structures were also tested for comparison. In dual matrix structures, results showed that the volume fraction of proeutectoid ferrite, new (epitaxial) ferrite, and ausferrite [bainitic ferrite + high-carbon austenite (stabilized or transformed austenite)] can be controlled to influence the strength and ductility. Generally, microvoids nucleation is initiated at the interface between the graphite nodules and the surrounding ferritic structure and at the grain boundary junctions in the fully ferritic microstructure. Debonding of the graphite nodules from the surrounding matrix structure was evident. The continuity of the ausferritic structure along the intercellular boundaries plays an important role in determining the fracture behavior of austempered ductile iron with different ausferrite volume fractions. The different fracture mechanisms correspond to the different levels of ausferrite volume fractions. With increasing continuity of the ausferritic structure, fracture pattern changed from ductile to moderate ductile nature. On the other hand, in the conventionally austempered samples with a fully ausferritic structure, the fracture mode was a mixture of quasi-cleavage and a dimple pattern. Microvoid coalescence was the dominant form of fracture in all structures.

  6. Computational prediction of cleavage using proteasomal in vitro digestion and MHC I ligand data

    Institute of Scientific and Technical Information of China (English)

    Yu-feng LU; Hao SHENG; Yi ZHANG; Zhi-yang LI


    Proteasomes are responsible for the production of the majority of cytotoxic T lymphocyte (CTL) epitopes.Hence,it is important to identify correctly which peptides will be generated by proteasomes from an unknown protein.However,the pool of proteasome cleavage data used in the prediction algorithms,whether from major histocompatibility complex (MHC) I ligand or in vitro digestion data,is not identical to in vivo proteasomal digestion products.Therefore,the accuracy and reliability of these models still need to be improved.In this paper,three types of proteasomal cleavage data,constitutive proteasome (cCP),immunoproteasome (iCP) in vitro cleavage,and MHC I ligandv data,were used for training cleave-site predictive methods based on the kernel-function stabilized matrix method (KSMM).The predictive accuracies of the KSMM+pair coefficients were 75.0%,72.3%,and 83.1% for cCP,iCP,and MHC I ligand data,respectively,which were comparable to the results from support vector machine (SVM).The three proteasomal cleavage methods were combined in turn with MHC I-peptide binding predictions to model MHC I-peptide processing and the presentation pathway.These integrations markedly improved MHC I peptide identification,increasing area under the receiver operator characteristics (ROC) curve (AUC) values from 0.82 to 0.91.The results suggested that both MHC I ligand and proteasomal in vitro degradation data can give an exact simulation of in vivo processed digestion.The information extracted from cCP and iCP in vitro cleavage data demonstrated that both cCP and iCP are selective in their usage of peptide bonds for cleavage.

  7. The potato carotenoid cleavage dioxygenase 4 catalyzes a single cleavage of β-ionone ring-containing carotenes and non-epoxidated xanthophylls

    KAUST Repository

    Bruno, Mark


    Down-regulation of the potato carotenoid cleavage dioxygenase 4 (StCCD4) transcript level led to tubers with altered morphology and sprouting activity, which also accumulated higher levels of violaxanthin and lutein leading to elevated carotenoid amounts. This phenotype indicates a role of this enzyme in tuber development, which may be exerted by a cleavage product. In this work, we investigated the enzymatic activity of StCCD4, by expressing the corresponding cDNA in carotenoid accumulating Escherichia coli strains and by performing in vitro assays with heterologously expressed enzyme. StCCD4 catalyzed the cleavage of all-. trans-β-carotene at the C9\\'-C10\\' double bond, leading to β-ionone and all-. trans-β-apo-10\\'-carotenal, both in vivo and in vitro. The enzyme also cleaved β,β-cryptoxanthin, zeaxanthin and lutein either at the C9\\'-C10\\' or the C9-C10 double bond in vitro. In contrast, we did not observe any conversion of violaxanthin and only traces of activity with 9-. cis-β-carotene, which led to 9-. cis-β-apo-10\\'-carotenal. Our data indicate that all-. trans-β-carotene is the likely substrate of StCCD4 in planta, and that this carotene may be precursor of an unknown compound involved in tuber development.

  8. Maisonneuve-hyperplantarflexion variant ankle fracture. (United States)

    Hinds, Richard M; Tran, Wesley H; Lorich, Dean G


    Maisonneuve fractures are rare ankle injuries, accounting for up to 7% of all ankle fractures. They consist of a proximal third fibula fracture, syndesmotic disruption, and medial ankle injury (either a deltoid ligament disruption or a medial malleolus fracture), and are often successfully managed with nonoperative treatment of the proximal fibula fracture and open reduction and internal fixation (ORIF) of the medial ankle injury and syndesmotic disruption. The hyperplantarflexion variant ankle fracture comprises approximately 7% of all ankle fractures and features dual posterior tibial lip fractures featuring a posterolateral fragment and a posteromedial fragment. Good functional results have been reported in the literature after ORIF of both the posterolateral and posteromedial fragments of this variant fracture that is not described by the Lauge-Hansen classification. In this report, the authors present the unique case of an isolated ankle fracture demonstrating characteristics of both a Maisonneuve fracture and a hyperplantarflexion variant ankle fracture. They also highlight the diagnostic imaging characteristics, including magnetic resonance imaging (MRI) and preoperative radiograph findings, surgical treatment, and postoperative clinical outcome for this patient with a Maisonneuve-hyperplantarflexion variant ankle fracture. To the authors' knowledge, this unique fracture pattern has not been reported previously in the literature. The authors conclude that although good results were seen postoperatively in this case, the importance of ORIF of both the posteromedial and posterolateral fragments of variant fractures cannot be overstated. They also found MRI to be a particularly helpful adjunct in formulating the correct diagnosis and treatment plan.

  9. Definition, classification and treatment of destructive fractures

    Institute of Scientific and Technical Information of China (English)

    FANG Guo-jun; QU Zhi-guo; LIU Zhuo; CHEN Yuan


    Destructive injury is defined as a very serious damage both to the bone and the soft tissues. But in clinical practice we found that in some fracture cases, the damage to soft tissues is not as severe as "destructive injury" indicates, whereas comminuted fractures still cannot show the severity of bone damage. Therefore we proposed a new term "destructive fractures" after combining the definition of destructive injury with typical clinic cases. Destructive fractures refer to the fractures whose osseous tissues are damaged too seriously to be repaired, but soft tissues, nerves and veins are less severely injured and can be repaired. From the year 2001 to 2010, 75 cases of destructive fractures were admitted in our department. According to whether the fractures interlinked with the external environment, together with the fracture sites, they were divided into 6 types: al type, closed diaphysis destructive fracture; a2 type, open diaphysis destructive fracture; b1 type, closed joint-involved destructive fracture; b2 type,open joint-involved destructive fracture; cl type, closed mixed destructive fracture; c2 type, open mixed destructive fracture. Corresponding clinical treatments were conducted for each type.The new classification criterion of destructivefracture is simple and practical and thus can be used as an important guide to make reasonable treatment plans for destructive fractures.

  10. 高温下钨断裂及氢影响钨断裂的分子动力学模拟%Molecular Dynamic Simulation of Fracture and Effect of Hydrogen on Fracture of Tungsten at High Temperature

    Institute of Scientific and Technical Information of China (English)

    欧阳义芳; 陈红梅; 钟夏平


    用分子动力学模拟在1000K温度下单晶钨在单轴应变的情形下断裂和氢对钨断裂的影响.结果表明:{100}面的辟裂比{110}面要容易.{100}面的辟裂与裂纹尖端的取向有关,模拟结果与低温下的实验结果符合得比较好.{(1)10}面方向的断裂不是辟裂方式.切应变的模拟结果也与实验相符.氢的加入对裂纹尖端影响比较大,能显著降低应力.%The fracture of Tungsten single crystal has been investigated under uniaxial strain at temperature 1000 K.The results indicate that the{100} plane cleaves more easily than the {110} plane.The cleavage of the {100}plane depends on the orientation of the crack-tip.The result is in good agreement with the experiment at low temperature. The simulation for the fracture of the ((1)10) indicates that the fracture mechanism is not cleavage. Two cases of shear strain are also studied.The present results are also coincident with available experiments of room temperature.The present results indicate that the fracture of Tungsten at high temperature is similar to that at low temperature. The effect of Hydrogen on the fracture is also discussed. It can affect the front of the crack-tip and decrease the yield stress.

  11. A study on the effect of nano-precipitates on fracture behavior of nano-structured Al-2wt%Cu alloy fabricated by accumulative roll bonding (ARB process

    Directory of Open Access Journals (Sweden)

    Azad B.


    Full Text Available An Al-2wt%Cu alloy was subjected to accumulative roll bonding (ARB process up to a strain of 4.8. The two kinds of different microstructures, i.e, solution treated (ST one and 190°C pre-aged for 30 min (Aged, were prepared as the starting structures for the ARB process. The microstructures were studied by transmission electron microscope (TEM and electron backscattering diffraction (EBSD. The results showed that the fine precipitates having the average particle size of 16 nm were formed after aging process. On the other hand, the mean grain size of the ST-ARB and the Aged-ARB specimens reached to 650 nm and 420 nm, respectively. Study of the fracture surfaces were carried out by scanning electron microscope (SEM. The results indicated that at 0-cycle ARB, the specimens show dimples indicating the micro-void coalescence (MVC mechanism of ductile fracture. The average size of dimples was larger in the ST-ARB specimen compared to the Aged-ARB specimen. The fracture mode was transgranular cleavage fracture in the Aged-specimen. At 3- cycle and 6-cycle ARB, also the specimens showed cleavage facets and river lines, that the river lines or the stress lines are steps between cleavage or parallel planes, which are always converged in the direction of local crack propagation.

  12. Reductive cleavage of nitrite to form terminal uranium mono-oxo complexes. (United States)

    Lewis, Andrew J; Carroll, Patrick J; Schelter, Eric J


    Uranium terminal mono-oxo complexes are prepared with a unique activation of nitrite following reductive cleavage of an N-O bond with loss of nitric oxide. The thermodynamic driving force of U═O bond formation differentiates this reactivity from known mechanisms of nitrite reduction, which are typically mediated by proton transfer. Mechanistic details are explored by DFT supporting a simple homolytic cleavage pathway from a κ(1)-ONO bound intermediate. Complexes of the formula U(VI)OX[N(SiMe(3))(2)](3) are formed providing a trigonal bipyramidal framework into which ligands trans to the U═O bond may be installed.

  13. Characterization of insulin-degrading enzyme-mediated cleavage of Aβ in distinct aggregation states. (United States)

    Hubin, Ellen; Cioffi, Federica; Rozenski, Jef; van Nuland, Nico A J; Broersen, Kerensa


    To enhance our understanding of the potential therapeutic utility of insulin-degrading enzyme (IDE) in Alzheimer's disease (AD), we studied in vitro IDE-mediated degradation of different amyloid-beta (Aβ) peptide aggregation states. Our findings show that IDE activity is driven by the dynamic equilibrium between Aβ monomers and higher ordered aggregates. We identify Met(35)-Val(36) as a novel IDE cleavage site in the Aβ sequence and show that Aβ fragments resulting from IDE cleavage form non-toxic amorphous aggregates. These findings need to be taken into account in therapeutic strategies designed to increase Aβ clearance in AD patients by modulating IDE activity.

  14. Computational analysis and modeling of cleavage by the immunoproteasome and the constitutive proteasome

    Directory of Open Access Journals (Sweden)

    Lafuente Esther M


    Full Text Available Abstract Background Proteasomes play a central role in the major histocompatibility class I (MHCI antigen processing pathway. They conduct the proteolytic degradation of proteins in the cytosol, generating the C-terminus of CD8 T cell epitopes and MHCI-peptide ligands (P1 residue of cleavage site. There are two types of proteasomes, the constitutive form, expressed in most cell types, and the immunoproteasome, which is constitutively expressed in mature dendritic cells. Protective CD8 T cell epitopes are likely generated by the immunoproteasome and the constitutive proteasome, and here we have modeled and analyzed the cleavage by these two proteases. Results We have modeled the immunoproteasome and proteasome cleavage sites upon two non-overlapping sets of peptides consisting of 553 CD8 T cell epitopes, naturally processed and restricted by human MHCI molecules, and 382 peptides eluted from human MHCI molecules, respectively, using N-grams. Cleavage models were generated considering different epitope and MHCI-eluted fragment lengths and the same number of C-terminal flanking residues. Models were evaluated in 5-fold cross-validation. Judging by the Mathew's Correlation Coefficient (MCC, optimal cleavage models for the proteasome (MCC = 0.43 ± 0.07 and the immunoproteasome (MCC = 0.36 ± 0.06 were obtained from 12-residue peptide fragments. Using an independent dataset consisting of 137 HIV1-specific CD8 T cell epitopes, the immunoproteasome and proteasome cleavage models achieved MCC values of 0.30 and 0.18, respectively, comparatively better than those achieved by related methods. Using ROC analyses, we have also shown that, combined with MHCI-peptide binding predictions, cleavage predictions by the immunoproteasome and proteasome models significantly increase the discovery rate of CD8 T cell epitopes restricted by different MHCI molecules, including A*0201, A*0301, A*2402, B*0702, B*2705. Conclusions We have developed models that are specific

  15. DNA Cleavage of the Copper(Ⅱ) Complexes with a Polyamine Ditopic Ligand

    Institute of Scientific and Technical Information of China (English)

    Yi Bin WEI; Pin YANG


    A new binuclear complex [Cu2L(OH)](ClO4)3·2H2O has been synthesized and characterized, where L=2,6-bis{[bis-(2-aminoethyl)amino]methyl}-benzene. In the presence of0.5 mmol/L complex at pH 8.10 and 37℃, the complex can efficiently cleavage pBR322 DNA with a rate constant kobs of 1.35 × 10-4 s-1. The cleavage occurred by a non-oxidative mechanism showing activity to be dependent on pH.

  16. Near-IR Light-Mediated Cleavage of Antibody-Drug Conjugates Using Cyanine Photocages. (United States)

    Nani, Roger R; Gorka, Alexander P; Nagaya, Tadanobu; Kobayashi, Hisataka; Schnermann, Martin J


    Despite significant progress in the clinical application of antibody drug conjugates (ADCs), novel cleavage strategies that provide improved selectivity are still needed. Herein is reported the first approach that uses near-IR light to cleave a small molecule from a biomacromolecule, and its application to the problem of ADC linkage. The preparation of cyanine antibody conjugates, drug cleavage mediated by 690 nm light, and initial in vitro and in vivo evaluation is described. These studies provide the critical chemical underpinning from which to develop this near-IR light cleavable linker strategy.

  17. Optimal scaling in ductile fracture (United States)

    Fokoua Djodom, Landry

    This work is concerned with the derivation of optimal scaling laws, in the sense of matching lower and upper bounds on the energy, for a solid undergoing ductile fracture. The specific problem considered concerns a material sample in the form of an infinite slab of finite thickness subjected to prescribed opening displacements on its two surfaces. The solid is assumed to obey deformation-theory of plasticity and, in order to further simplify the analysis, we assume isotropic rigid-plastic deformations with zero plastic spin. When hardening exponents are given values consistent with observation, the energy is found to exhibit sublinear growth. We regularize the energy through the addition of nonlocal energy terms of the strain-gradient plasticity type. This nonlocal regularization has the effect of introducing an intrinsic length scale into the energy. We also put forth a physical argument that identifies the intrinsic length and suggests a linear growth of the nonlocal energy. Under these assumptions, ductile fracture emerges as the net result of two competing effects: whereas the sublinear growth of the local energy promotes localization of deformation to failure planes, the nonlocal regularization stabilizes this process, thus resulting in an orderly progression towards failure and a well-defined specific fracture energy. The optimal scaling laws derived here show that ductile fracture results from localization of deformations to void sheets, and that it requires a well-defined energy per unit fracture area. In particular, fractal modes of fracture are ruled out under the assumptions of the analysis. The optimal scaling laws additionally show that ductile fracture is cohesive in nature, i.e., it obeys a well-defined relation between tractions and opening displacements. Finally, the scaling laws supply a link between micromechanical properties and macroscopic fracture properties. In particular, they reveal the relative roles that surface energy and microplasticity

  18. Active site specificity profiling of the matrix metalloproteinase family: Proteomic identification of 4300 cleavage sites by nine MMPs explored with structural and synthetic peptide cleavage analyses. (United States)

    Eckhard, Ulrich; Huesgen, Pitter F; Schilling, Oliver; Bellac, Caroline L; Butler, Georgina S; Cox, Jennifer H; Dufour, Antoine; Goebeler, Verena; Kappelhoff, Reinhild; Keller, Ulrich Auf dem; Klein, Theo; Lange, Philipp F; Marino, Giada; Morrison, Charlotte J; Prudova, Anna; Rodriguez, David; Starr, Amanda E; Wang, Yili; Overall, Christopher M


    Secreted and membrane tethered matrix metalloproteinases (MMPs) are key homeostatic proteases regulating the extracellular signaling and structural matrix environment of cells and tissues. For drug targeting of proteases, selectivity for individual molecules is highly desired and can be met by high yield active site specificity profiling. Using the high throughput Proteomic Identification of protease Cleavage Sites (PICS) method to simultaneously profile both the prime and non-prime sides of the cleavage sites of nine human MMPs, we identified more than 4300 cleavages from P6 to P6' in biologically diverse human peptide libraries. MMP specificity and kinetic efficiency were mainly guided by aliphatic and aromatic residues in P1' (with a ~32-93% preference for leucine depending on the MMP), and basic and small residues in P2' and P3', respectively. A wide differential preference for the hallmark P3 proline was found between MMPs ranging from 15 to 46%, yet when combined in the same peptide with the universally preferred P1' leucine, an unexpected negative cooperativity emerged. This was not observed in previous studies, probably due to the paucity of approaches that profile both the prime and non-prime sides together, and the masking of subsite cooperativity effects by global heat maps and iceLogos. These caveats make it critical to check for these biologically highly important effects by fixing all 20 amino acids one-by-one in the respective subsites and thorough assessing of the inferred specificity logo changes. Indeed an analysis of bona fide MEROPS physiological substrate cleavage data revealed that of the 37 natural substrates with either a P3-Pro or a P1'-Leu only 5 shared both features, confirming the PICS data. Upon probing with several new quenched-fluorescent peptides, rationally designed on our specificity data, the negative cooperativity was explained by reduced non-prime side flexibility constraining accommodation of the rigidifying P3 proline with

  19. Fracture Union in Closed Interlocking Nail in Humeral Shaft Fractures

    Institute of Scientific and Technical Information of China (English)

    Ramji Lal Sahu; Rajni Ranjan; Ajay Lal


    Background:Fracture shaft humerus is a major cause of morbidity in patients with upper extremity injuries.The aim of this study was to evaluate the outcome of interlocking nail in humeral shaft fractures.Methods:This study was conducted in the Department of Orthopedic Surgery in SMS and R Sharda University from January 2010 to November 2013.Seventy-eight patients were recruited from emergency and out-patient department having a close fracture of humerus shaft.All patients were operated under general anesthesia and closed reamed interlocking nailing was done.All patients were followed for 9 months.Results:Out of 78 patients,69 patients underwent union in 90-150 days with a mean of 110.68 days.Complications found in four patients who had nonunion,and five patients had delayed union,which was treated with bone grafting.All the patients were assessed clinically and radiologically for fracture healing,joint movements and implant failure.The results were excellent in 88.46% and good in 6.41% patients.Complete subjective,functional,and clinical recovery had occurred in almost 100% of the patients.Conclusions:The results of the present study indicates that in the presence of proper indications,reamed antegrade intramedullary interlocked nailing appears to be a method of choice for internal fixation of osteoporotic and pathologic fractures.

  20. A 3-Dimensional discrete fracture network generator to examine fracture-matrix interaction using TOUGH2

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Kazumasa; Yongkoo, Seol


    Water fluxes in unsaturated, fractured rock involve the physical processes occurring at fracture-matrix interfaces within fracture networks. Modeling these water fluxes using a discrete fracture network model is a complicated effort. Existing preprocessors for TOUGH2 are not suitable to generate grids for fracture networks with various orientations and inclinations. There are several 3-D discrete-fracture-network simulators for flow and transport, but most of them do not capture fracture-matrix interaction. We have developed a new 3-D discrete-fracture-network mesh generator, FRACMESH, to provide TOUGH2 with information about the fracture network configuration and fracture-matrix interactions. FRACMESH transforms a discrete fracture network into a 3 dimensional uniform mesh, in which fractures are considered as elements with unique rock material properties and connected to surrounding matrix elements. Using FRACMESH, individual fractures may have uniform or random aperture distributions to consider heterogeneity. Fracture element volumes and interfacial areas are calculated from fracture geometry within individual elements. By using FRACMESH and TOUGH2, fractures with various inclinations and orientations, and fracture-matrix interaction, can be incorporated. In this paper, results of flow and transport simulations in a fractured rock block utilizing FRACMESH are presented.


    Institute of Scientific and Technical Information of China (English)

    Yang Xinhua; Chen Chuanyao; Hu Yuantai; Wang Cheng


    Mechanical and electrical damages are introduced to study the fracture mechanics of piezoelectric ceramics in this paper. Two kinds of piezoelectric fracture criteria are established using the method of least squares combined with a damage analysis of the well-known piezoelectric fracture experiments of Park and Sun's. One is based on a linear combination of the mechanical and electrical damages and the other on their nonlinear combination. When the combined damage D is up to its critical value Dc, piezoelectric fracture occurs. It is found from the qualitative comparison of the numerical results with the experimental data that the nonlinearly combined damage fracture criterion can give a better prediction of piezoelectric fracture. And it is concluded from the nonlinearly combined damage fracture criterion that a negative electric field impedes fracture whereas the effect of a positive electric field on fracture depends on its magnitude.

  2. Growth Kinematics of Opening-Mode Fractures (United States)

    Eichhubl, P.; Alzayer, Y.; Laubach, S.; Fall, A.


    Fracture aperture is a primary control on flow in fractured reservoirs of low matrix permeability including unconventional oil and gas reservoirs and most geothermal systems. Guided by principles of linear elastic fracture mechanics, fracture aperture is generally assumed to be a linear function of fracture length and elastic material properties. Natural opening-mode fractures with significant preserved aperture are observed in core and outcrop indicative of fracture opening strain accommodated by permanent solution-precipitation creep. Fracture opening may thus be decoupled from length growth if the material effectively weakens after initial elastic fracture growth by either non-elastic deformation processes or changes in elastic properties. To investigate the kinematics of fracture length and aperture growth, we reconstructed the opening history of three opening-mode fractures that are bridged by crack-seal quartz cement in Travis Peak Sandstone of the SFOT-1 well, East Texas. Similar crack-seal cement bridges had been interpreted to form by repeated incremental fracture opening and subsequent precipitation of quartz cement. We imaged crack-seal cement textures for bridges sampled at varying distance from the tips using scanning electron microscope cathodoluminescence, and determined the number and thickness of crack-seal cement increments as a function of position along the fracture length and height. Observed trends in increment number and thickness are consistent with an initial stage of fast fracture propagation relative to aperture growth, followed by a stage of slow propagation and pronounced aperture growth. Consistent with fluid inclusion observations indicative of fracture opening and propagation occurring over 30-40 m.y., we interpret the second phase of pronounced aperture growth to result from fracture opening strain accommodated by solution-precipitation creep and concurrent slow, possibly subcritical, fracture propagation. Similar deformation

  3. Effect of T-stress on the cleavage crack growth resistance resulting from plastic flow

    DEFF Research Database (Denmark)

    Tvergaard, Viggo


    Crack growth is studied numerically for cases where fracture occurs by atomic separation, sc that the length scale of the fracture process is typically much smaller than the dislocation spacing. Thus, the crack growth mechanism is brittle, but due to plastic flow at some distance from the crack t...

  4. Fracture assessment of the Oskarshamn 1 reactor pressure vessel under cold over-pressurization

    Energy Technology Data Exchange (ETDEWEB)

    Sattari-Far, I. [DNV Technical Consulting AB, Stockholm (Sweden)


    The major motivation of this study was to develop a methodology for fracture assessment of surface defects in the 01 reactor pressure vessel under cold loading scenarios, particularly the cold over-pressurization event. According to a previous study, the FENIX project, the cold over-pressurization of the O1 reactor is a limiting loading case, as the ductile/brittle transition temperature (RT{sub NDT}) of certain welds in the O1 beltline region may be over 100 deg C at the-end-of-life condition. The FENIX project gave values of the acceptable and critical crack depth to be equal to the thickness of the cladding layer (about 6 mm) under this load case using the ASME K{sub Ic} reference curve methodology. This study is aimed to develop a methodology to give a more precise fracture assessment of the O1 reactor under cold loading scenarios. Some of the main objectives of this study have been as below: To prepare a material which can simulate the mechanical properties and RT{sub NDT} of the O1 reactor at the end-of-life conditions. To conduct a fracture mechanics test program to cover the essential influencing factors, such as crack geometry (shallow and deep cracks) and loading condition (uniaxial and biaxial) on the cleavage fracture toughness. To perform fracture mechanics analyses to identify a suitable methodology for assessment of the experimental results. To study the responses of engineering fracture assessment methods to the experimental results from the clad specimens. To propose a fracture assessment procedure for determination of the acceptable and critical flaw sizes in the 01 reactor under the cold loading events. A test program consisted of experiments on standard SEN(B) specimens and clad beams, containing surface cracks was conducted during the course of this project. A total of nine clad beams and clad cruciform specimens were tested under uniaxial and biaxial loading. The test material is reactor steel of type A 508 Grade B, which is specially heat

  5. Electrochemical Protein Cleavage in a Microfluidic Cell with Integrated Boron Doped Diamond Electrodes

    NARCIS (Netherlands)

    van den Brink, Floris T G; Zhang, Tao; Ma, Liwei; Bomer, Johan; Odijk, Mathieu; Olthuis, Wouter; Permentier, Hjalmar P; Bischoff, Rainer; van den Berg, Albert


    Specific electrochemical cleavage of peptide bonds at the C-terminal side of tyrosine and tryptophan generates peptides amenable to liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis for protein identification. To this end we developed a microfluidic electrochemical cell of 160 nL vo

  6. Site-specifically Hydrolytic Cleavage of Oxidized Insulin B Chain With Cu(II) Ion

    Institute of Scientific and Technical Information of China (English)


    Electrospray mass spectrometry investigation shows that denatured oxidized insulin B chain can be selectively cleaved by simple Cu(II) ion and the site of cleavage is at Gly8-Ser9 bond which is second amide bond left from His 10 in the sequence of oxidized insulin B chain.

  7. A Python analytical pipeline to identify prohormone precursors and predict prohormone cleavage sites

    Directory of Open Access Journals (Sweden)

    Bruce Southey


    Full Text Available Neuropeptides and hormones are signaling molecules that support cell-cell communication in the central nervous system. Experimentally characterizing neuropeptides requires significant efforts because of the complex and variable processing of prohormone precursor proteins into neuropeptides and hormones. We demonstrate the power and flexibility of the Python language to develop components of an bioinformatic analytical pipeline to identify precursors from genomic data and to predict cleavage as these precursors are en route to the final bioactive peptides. We identified 75 precursors in the rhesus genome, predicted cleavage sites using support vector machines and compared the rhesus predictions to putative assignments based on homology to human sequences. The correct classification rate of cleavage using the support vector machines was over 97% for both human and rhesus data sets. The functionality of Python has been important to develop and maintain NeuroPred (, a user-centered web application for the neuroscience community that provides cleavage site prediction from a wide range of models, precision and accuracy statistics, post-translational modifications, and the molecular mass of potential peptides. The combined results illustrate the suitability of the Python language to implement an all-inclusive bioinformatics approach to predict neuropeptides that encompasses a large number of interdependent steps, from scanning genomes for precursor genes to identification of potential bioactive neuropeptides.

  8. A python analytical pipeline to identify prohormone precursors and predict prohormone cleavage sites. (United States)

    Southey, Bruce R; Sweedler, Jonathan V; Rodriguez-Zas, Sandra L


    Neuropeptides and hormones are signaling molecules that support cell-cell communication in the central nervous system. Experimentally characterizing neuropeptides requires significant efforts because of the complex and variable processing of prohormone precursor proteins into neuropeptides and hormones. We demonstrate the power and flexibility of the Python language to develop components of an bioinformatic analytical pipeline to identify precursors from genomic data and to predict cleavage as these precursors are en route to the final bioactive peptides. We identified 75 precursors in the rhesus genome, predicted cleavage sites using support vector machines and compared the rhesus predictions to putative assignments based on homology to human sequences. The correct classification rate of cleavage using the support vector machines was over 97% for both human and rhesus data sets. The functionality of Python has been important to develop and maintain NeuroPred (, a user-centered web application for the neuroscience community that provides cleavage site prediction from a wide range of models, precision and accuracy statistics, post-translational modifications, and the molecular mass of potential peptides. The combined results illustrate the suitability of the Python language to implement an all-inclusive bioinformatics approach to predict neuropeptides that encompasses a large number of interdependent steps, from scanning genomes for precursor genes to identification of potential bioactive neuropeptides.

  9. Facile P-C/C-H Bond-Cleavage Reactivity of Nickel Bis(diphosphine) Complexes

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Shaoguang [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Li, Haixia [Texas A & M Univ., College Station, TX (United States). Dept. of Chemistry; Appel, Aaron M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hall, Michael B. [Texas A & M Univ., College Station, TX (United States). Dept. of Chemistry; Bullock, R. Morris [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)


    Unusual cleavage of P-C and C-H bonds of the P2N2 ligand in heteroleptic [Ni(P2N2)(diphosphine)]2+ complexes results in the formation of an iminium formyl nickelate featuring a C,P,P-tridentate coordination mode.

  10. Probing Electron-Induced Bond Cleavage at the Single-Molecule Level Using DNA Origami Templates

    DEFF Research Database (Denmark)

    Keller, Adrian Clemens; Bald, Ilko; Rotaru, Alexandru;


    specifically designed oligonucleotide targets that are attached to DNA origami templates. In this way, we use a highly selective approach to compare the efficiency of the electron-induced dissociation of a single disulfide bond with the more complex cleavage of the DNA backbone within a TT dinucleotide...

  11. DNA cleavage enzymes for treatment of persistent viral infections: Recent advances and the pathway forward

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Nicholas D., E-mail: [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Department of Laboratory Medicine, University of Washington, Seattle, WA 98195 (United States); Aubert, Martine, E-mail: [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Dang, Chung H., E-mail: [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Stone, Daniel, E-mail: [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Jerome, Keith R., E-mail: [Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E5-110, Seattle, WA 98109 (United States); Department of Laboratory Medicine, University of Washington, Seattle, WA 98195 (United States); Department of Microbiology, University of Washington, Seattle, WA 98195 (United States)


    Treatment for most persistent viral infections consists of palliative drug options rather than curative approaches. This is often because long-lasting viral DNA in infected cells is not affected by current antivirals, providing a source for viral persistence and reactivation. Targeting latent viral DNA itself could therefore provide a basis for novel curative strategies. DNA cleavage enzymes can be used to induce targeted mutagenesis of specific genes, including those of exogenous viruses. Although initial in vitro and even in vivo studies have been carried out using DNA cleavage enzymes targeting various viruses, many questions still remain concerning the feasibility of these strategies as they transition into preclinical research. Here, we review the most recent findings on DNA cleavage enzymes for human viral infections, consider the most relevant animal models for several human viral infections, and address issues regarding safety and enzyme delivery. Results from well-designed in vivo studies will ideally provide answers to the most urgent remaining questions, and allow continued progress toward clinical application. - Highlights: • Recent in vitro and in vivo results for DNA cleavage enzymes targeting persistent viral infections. • Analysis of the best animal models for testing enzymes for HBV, HSV, HIV and HPV. • Challenges facing in vivo delivery of therapeutic enzymes for persistent viral infections. • Safety issues to be addressed with proper animal studies.

  12. Proximity-activated nanoparticles: in vitro performance of specific structural modification by enzymatic cleavage

    Directory of Open Access Journals (Sweden)

    R Adam Smith


    Full Text Available R Adam Smith, Sarah L Sewell, Todd D GiorgioDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USAAbstract: The development and in vitro performance of a modular nanoscale system capable of specific structural modification by enzymatic activity is described in this work. Due to its small physical size and adaptable characteristics, this system has the potential for utilization in targeted delivery systems and biosensing. Nanoparticle probes were synthesized containing two distinct fluorescent species including a quantum dot base particle and fluorescently labeled cleavable peptide substrate. Activity of these probes was monitored by gel electrophoresis with quantitative cleavage measurements made by fluorometric analysis. The model proximity-activated nanoparticles studied here exhibit significant susceptibility to cleavage by matrix metalloprotease-7 (MMP-7 at physiologically relevant concentrations, with nearly complete cleavage of available substrate molecules after 24 hours. This response is specific to MMP-7 enzyme activity, as cleavage is completely inhibited with the addition of EDTA. Utilization of enzyme-specific modification is a sensitive approach with broad applications for targeted therapeutics and biosensing. The versatility of this nanoparticle system is highlighted in its modular design, as it has the capability to integrate characteristics for detection, biosensing, targeting, and payload delivery into a single, multifunctional nanoparticle structure.Keywords: quantum dot, MMP-7, protease, proximity activated nanoparticle

  13. Unusual nickel-mediated C-S cleavage of alkyl and aryl sulfoxides. (United States)

    Schaub, Thomas; Backes, Marc; Radius, Udo


    The first examples of transition metal mediated C-S cleavage of sulfoxides containing sp2- and sp3-hybridized carbon bonds attached to the sulfur atom and the first example of a structurally characterized complex featuring an oxygen-bound sulfinyl ligand are presented.

  14. Antisense oligonucleotide-mediated exon skipping as a strategy to reduce proteolytic cleavage of ataxin-3. (United States)

    Toonen, Lodewijk J A; Schmidt, Iris; Luijsterburg, Martijn S; van Attikum, Haico; van Roon-Mom, Willeke M C


    Spinocerebellar ataxia type-3 (SCA3) is a neurodegenerative disorder caused by a polyglutamine repeat expansion in the ataxin-3 protein. Cleavage of mutant ataxin-3 by proteolytic enzymes yields ataxin-3 fragments containing the polyglutamine stretch. These shorter ataxin-3 fragments are thought to be involved in SCA3 pathogenesis due to their increased cellular toxicity and their involvement in formation of the characteristic neuronal aggregates. As a strategy to prevent formation of toxic cleavage fragments, we investigated an antisense oligonucleotide-mediated modification of the ataxin-3 pre-mRNA through exon skipping of exon 8 and 9, resulting in the removal of a central 88 amino acid region of the ataxin-3 protein. This removed protein region contains several predicted cleavage sites and two ubiquitin-interacting motifs. In contrast to unmodified mutant ataxin-3, the internally truncated ataxin-3 protein did not give rise to potentially toxic cleavage fragments when incubated with caspases. In vitro experiments did not show cellular toxicity of the modified ataxin-3 protein. However, the modified protein was incapable of binding poly-ubiquitin chains, which may interfere with its normal deubiquitinating function. Low exon skipping efficiencies combined with reduction in important ataxin-3 protein functions suggest that skipping of exon 8 and 9 is not a viable therapeutic option for SCA3.

  15. Metabolic Engineering to Develop a Pathway for the Selective Cleavage of Carbon-Nitrogen Bonds

    Energy Technology Data Exchange (ETDEWEB)

    John J. Kilbane II


    The objective of the project is to develop a biochemical pathway for the selective cleavage of C-N bonds in molecules found in petroleum. Specifically a novel biochemical pathway will be developed for the selective cleavage of C-N bonds in carbazole. The cleavage of the first C-N bond in carbazole is accomplished by the enzyme carbazole dioxygenase, that catalyzes the conversion of carbazole to 2-aminobiphenyl-2,3-diol. The genes encoding carbazole dioxygenase were cloned from Sphingomonas sp. GTIN11 and from Pseudomonas resinovorans CA10. The selective cleavage of the second C-N bond has been challenging, and efforts to overcome that challenge have been the focus of recent research in this project. Enrichment culture experiments succeeded in isolating bacterial cultures that can metabolize 2-aminobiphenyl, but no enzyme capable of selectively cleaving the C-N bond in 2-aminobiphenyl has been identified. Aniline is very similar to the structure of 2-aminobiphenyl and aniline dioxygenase catalyzes the conversion of aniline to catechol and ammonia. For the remainder of the project the emphasis of research will be to simultaneously express the genes for carbazole dioxygenase and for aniline dioxygenase in the same bacterial host and then to select for derivative cultures capable of using carbazole as the sole source of nitrogen.

  16. Quercetin-Iron Complex: Synthesis, Characterization, Antioxidant, DNA Binding, DNA Cleavage, and Antibacterial Activity Studies. (United States)

    Raza, Aun; Xu, Xiuquan; Xia, Li; Xia, Changkun; Tang, Jian; Ouyang, Zhen


    Quercetin-iron (II) complex was synthesized and characterized by elemental analysis, ultraviolet-visible spectrophotometry, fourier transform infrared spectroscopy, mass spectrometry, proton nuclear magnetic resonance spectroscopy, thermogravimetry and differential scanning calorimetry, scanning electron micrography and molar conductivity. The low molar conductivity value investigates the non-electrolyte nature of the complex. The elemental analysis and other physical and spectroscopic methods reveal the 1:2 stoichiometric ratio (metal:ligand) of the complex. Antioxidant study of the quercetin and its metal complex against 2, 2-di-phenyl-1-picryl hydrazyl radical showed that the complex has much more radical scavenging activity than free quercetin. The interaction of quercetin-iron (II) complex with DNA was determined using ultraviolet visible spectra, fluorescence spectra and agarose gel electrophoresis. The results showed that quercetin-iron (II) complex can intercalate moderately with DNA, quench a strong intercalator ethidium bromide and compete for the intercalative binding sites. The complex showed significant cleavage of pBR 322 DNA from supercoiled form to nicked circular form and these cleavage effects were dose-dependent. Moreover, the mechanism of DNA cleavage indicated that it was an oxidative cleavage pathway. These results revealed the potential nuclease activity of complex to cleave DNA. In addition, antibacterial activity of complex on E.coli and S. aureus was also investigated. The results showed that complex has higher antibacterial activity than ligand.

  17. Rutin-Nickel Complex: Synthesis, Characterization, Antioxidant, DNA Binding, and DNA Cleavage Activities. (United States)

    Raza, Aun; Bano, Shumaila; Xu, Xiuquan; Zhang, Rong Xian; Khalid, Haider; Iqbal, Furqan Muhammad; Xia, Changkun; Tang, Jian; Ouyang, Zhen


    The rutin-nickel (II) complex (RN) was synthesized and characterized by elemental analysis, UV-visible spectroscopy, IR, mass spectrometry, (1)H NMR, TG-DSC, SEM, and molar conductivity. The low molar conductivity value investigates the non-electrolyte nature of the complex. The elemental analysis and other physical and spectroscopic methods reveal the 1:2 stoichiometric ratio (metal/ligand) of the complex. An antioxidant study of rutin and its metal complex against DPPH radical showed that the complex has more radical scavenging activity than free rutin. The interaction of complex RN with DNA was determined using fluorescence spectra and agarose gel electrophoresis. The results showed that RN can intercalate moderately with DNA, quench a strong intercalator ethidium bromide (EB), and compete for the intercalative binding sites. The complex showed significant cleavage of pBR 322 DNA from supercoiled form (SC) to nicked circular form (NC), and these cleavage effects were dose-dependent. Moreover, the mechanism of DNA cleavage indicated that it was a hydrolytic cleavage pathway. These results revealed the potential nuclease activity of the complex to cleave DNA.

  18. Efficient Nuclear DNA Cleavage in Human Cancer Cells by Synthetic Bleomycin Mimics

    NARCIS (Netherlands)

    Li, Qian; van der Wijst, Monique G. P.; Kazemier, Hinke G.; Rots, Marianne G.; Roelfes, Gerard


    Iron complexes of N,N-bis(2-Pyridylmethyl)-N-bis(2-pyridyl)-methylamine (N4Py) have proven to be excellent synthetic mimics of the Bleomycins (BLMs), which are a family of natural antibiotics used clinically in the treatment of certain cancers. However, most investigations of DNA cleavage activity o

  19. A novel purification method for histidine-tagged proteins containing a thrombin cleavage site

    NARCIS (Netherlands)

    Hefti, M.H.; Vugt-Toorn, van der C.J.; Dixon, R.; Vervoort, J.J.M.


    A general procedure for the purification of histidine-tagged proteins has been developed using immobilized metal-ion affinity chromatography. This two-step purification method can be used for proteins containing a hexahistidine tag and a thrombin cleavage site, yielding high amounts of purified prot

  20. Cleavage mediated by the catalytic domain of bacterial RNase P RNA. (United States)

    Wu, Shiying; Kikovska, Ema; Lindell, Magnus; Kirsebom, Leif A


    Like other RNA molecules, RNase P RNA (RPR) is composed of domains, and these have different functions. Here, we provide data demonstrating that the catalytic (C) domain of Escherichia coli (Eco) RPR when separated from the specificity (S) domain mediates cleavage using various model RNA hairpin loop substrates. Compared to full-length Eco RPR, the rate constant, k(obs), of cleavage for the truncated RPR (CP RPR) was reduced 30- to 13,000-fold depending on substrate. Specifically, the structural architecture of the -1/+73 played a significant role where a C(-1)/G(+73) pair had the most dramatic effect on k(obs). Substitution of A(248) (E. coli numbering), positioned near the cleavage site in the RNase P-substrate complex, with G in the CP RPR resulted in 30-fold improvement in rate. In contrast, strengthening the interaction between the RPR and the 3' end of the substrate only had a modest effect. Interestingly, although deleting the S-domain gave a reduction in the rate, it resulted in a less erroneous RPR with respect to cleavage site selection. These data support and extend our understanding of the coupling between the distal interaction between the S-domain and events at the active site. Our findings will also be discussed with respect to the structure of RPR derived from different organisms.

  1. The N-terminal domain allosterically regulates cleavage and activation of the epithelial sodium channel. (United States)

    Kota, Pradeep; Buchner, Ginka; Chakraborty, Hirak; Dang, Yan L; He, Hong; Garcia, Guilherme J M; Kubelka, Jan; Gentzsch, Martina; Stutts, M Jackson; Dokholyan, Nikolay V


    The epithelial sodium channel (ENaC) is activated upon endoproteolytic cleavage of specific segments in the extracellular domains of the α- and γ-subunits. Cleavage is accomplished by intracellular proteases prior to membrane insertion and by surface-expressed or extracellular soluble proteases once ENaC resides at the cell surface. These cleavage events are partially regulated by intracellular signaling through an unknown allosteric mechanism. Here, using a combination of computational and experimental techniques, we show that the intracellular N terminus of γ-ENaC undergoes secondary structural transitions upon interaction with phosphoinositides. From ab initio folding simulations of the N termini in the presence and absence of phosphatidylinositol 4,5-bisphosphate (PIP2), we found that PIP2 increases α-helical propensity in the N terminus of γ-ENaC. Electrophysiology and mutation experiments revealed that a highly conserved cluster of lysines in the γ-ENaC N terminus regulates accessibility of extracellular cleavage sites in γ-ENaC. We also show that conditions that decrease PIP2 or enhance ubiquitination sharply limit access of the γ-ENaC extracellular domain to proteases. Further, the efficiency of allosteric control of ENaC proteolysis is dependent on Tyr(370) in γ-ENaC. Our findings provide an allosteric mechanism for ENaC activation regulated by the N termini and sheds light on a potential general mechanism of channel and receptor activation.

  2. The N-terminal Domain Allosterically Regulates Cleavage and Activation of the Epithelial Sodium Channel* (United States)

    Kota, Pradeep; Buchner, Ginka; Chakraborty, Hirak; Dang, Yan L.; He, Hong; Garcia, Guilherme J. M.; Kubelka, Jan; Gentzsch, Martina; Stutts, M. Jackson; Dokholyan, Nikolay V.


    The epithelial sodium channel (ENaC) is activated upon endoproteolytic cleavage of specific segments in the extracellular domains of the α- and γ-subunits. Cleavage is accomplished by intracellular proteases prior to membrane insertion and by surface-expressed or extracellular soluble proteases once ENaC resides at the cell surface. These cleavage events are partially regulated by intracellular signaling through an unknown allosteric mechanism. Here, using a combination of computational and experimental techniques, we show that the intracellular N terminus of γ-ENaC undergoes secondary structural transitions upon interaction with phosphoinositides. From ab initio folding simulations of the N termini in the presence and absence of phosphatidylinositol 4,5-bisphosphate (PIP2), we found that PIP2 increases α-helical propensity in the N terminus of γ-ENaC. Electrophysiology and mutation experiments revealed that a highly conserved cluster of lysines in the γ-ENaC N terminus regulates accessibility of extracellular cleavage sites in γ-ENaC. We also show that conditions that decrease PIP2 or enhance ubiquitination sharply limit access of the γ-ENaC extracellular domain to proteases. Further, the efficiency of allosteric control of ENaC proteolysis is dependent on Tyr370 in γ-ENaC. Our findings provide an allosteric mechanism for ENaC activation regulated by the N termini and sheds light on a potential general mechanism of channel and receptor activation. PMID:24973914

  3. Oxidative cleavage of erucic acid for the synthesis of brassylic acid

    Energy Technology Data Exchange (ETDEWEB)

    Mohammed J. Nasrullah; Pooja Thapliyal; Erica N. Pfarr; Nicholas S. Dusek; Kristofer L. Schiele; James A. Bahr


    The main focus of this work is to synthesize Brassylic Acid (BA) using oxidative cleavage of Erucic Acid (EA). Crambe (Crambe abyssinica) is an industrial oilseed grown in North Dakota. Crambe has potential as an industrial fatty acid feedstock as a source of Erucic acid (EA). It has approximately 50-60 % of EA, a C{sub 22} monounsaturated fatty acid. Oxidative cleavage of unsaturated fatty acids derived from oilseeds produces long chain (9, 11, and 13 carbon atoms) dibasic and monobasic acids. These acids are known commercial feedstocks for the preparation of nylons, polyesters, waxes, surfactants, and perfumes. Other sources of EA are Rapeseed seed oil which 50-60 % of EA. Rapeseed is grown outside USA. The oxidative cleavage of EA was done using a high throughput parallel pressure reactor system. Kinetics of the reaction shows that BA yields reach a saturation at 12 hours. H{sub 2}WO{sub 4} was found to be the best catalyst for the oxidative cleavage of EA. High yields of BA were obtained at 80 C with bubbling of O{sub 2} or 10 bar of O{sub 2} for 12 hours.

  4. Cleavage of resveratrol in fungi: characterization of the enzyme Rco1 from Ustilago maydis. (United States)

    Brefort, Thomas; Scherzinger, Daniel; Limón, M Carmen; Estrada, Alejandro F; Trautmann, Danika; Mengel, Carina; Avalos, Javier; Al-Babili, Salim


    Ustilago maydis, the causative agent of corn smut disease, contains two genes encoding members of the carotenoid cleavage oxygenase family, a group of enzymes that cleave double bonds in different substrates. One of them, Cco1, was formerly identified as a β-carotene cleaving enzyme. Here we elucidate the function of the protein encoded by the second gene, termed here as Ustilago maydis Resveratrol cleavage oxygenase 1 (Um Rco1). In vitro incubations of heterologously expressed and purified UM Rco1 with different carotenoid and stilbene substrates demonstrate that it cleaves the interphenyl Cα-Cβ double bond of the phytoalexin resveratrol and its derivative piceatannol. Um Rco1 exhibits a high degree of substrate specificity, as suggested by the lack of activity on carotenoids and the other resveratrol-related compounds tested. The activity of Um Rco1 was confirmed by incubation of U. maydis rco1 deletion and over-expression strains with resveratrol. Furthermore, treatment with resveratrol resulted in striking alterations of cell morphology. However, pathogenicity assays indicated that Um rco1 is largely dispensable for biotrophic development. Our work reveals Um Rco1 as the first eukaryotic resveratrol cleavage enzyme identified so far. Moreover, Um Rco1 represents a subfamily of fungal enzymes likely involved in the degradation of stilbene compounds, as suggested by the cleavage of resveratrol by homologs from Aspergillus fumigatus, Chaetomium globosum and Botryotinia fuckeliana.

  5. Arthrobacter luteus restriction endonuclease cleavage map of X174 RF DNA

    NARCIS (Netherlands)

    Vereijken, J.M.; Mansfeld, A.D.M. van; Baas, P.D.; Jansz, H.S.


    Cleavage of X174 RF DNA with the restriction endonuclease from Arthrobacter luteus (Alu I) produces 23 fragments of approximately 24–1100 base pairs in length. The order of most of these fragments has been established by digestion of Haemophilus influenzae Rd (Hind II) and Haemophilus aegyptius (Hae

  6. Carbon-Carbon Bond Cleavage Reaction: Synthesis of Multisubstituted Pyrazolo[1,5-a]pyrimidines. (United States)

    Saikia, Pallabi; Gogoi, Sanjib; Boruah, Romesh C


    A new carbon-carbon bond cleavage reaction was developed for the efficient synthesis of multisubstituted pyrazolo[1,5-a]pyrimidines. This base induced reaction of 1,3,5-trisubstituted pentane-1,5-diones and substituted pyrazoles afforded good yields of the pyrazolo[1,5-a]pyrimidines.

  7. The party politics of economic reform: Public opinion, party positions and partisan cleavages

    NARCIS (Netherlands)

    Padgett, Stephen


    This article focuses on the capacity of parties to cultivate public opinion to accept welfare state reform. 'Preference shaping', it is argued, depends on the intensity of party 'messages', which will be at their strongest where there are sharply defined partisan cleavages in opinion. The aversion o

  8. Caspase-Dependent Apoptosis Induced by Telomere Cleavage and TRF2 Loss

    Directory of Open Access Journals (Sweden)

    Asha S. Multani


    Full Text Available Chromosomal abnormalities involving telomeric associations (TAs often precede replicative senescence and abnormal chromosome configurations. We report here that telomere cleavage following exposure to proapoptotic agents is an early event in apoptosis. Exposure of human and murine cancer cells to a variety of pro-apoptotic stimuli (staurosporine, thapsigargin, anti-Fas antibody, cancer chemotherapeutic agents resulted in telomere cleavage and aggregation, finally their extrusion from the nuclei. Telomere loss was associated with arrest of cells in G2/M phase and preceded DNA fragmentation. Telomere erosion and subsequent large-scale chromatin cleavage were inhibited by overexpression of the anti -apoptotic protein, bcl-2, two peptide caspase inhibitors (BACMK and zVADfmk, indicating that both events are regulated by caspase activation. The results demonstrate that telomere cleavage is an early chromatin alteration detected in various cancer cell lines leading to drug-induced apoptosis, suggest that this event contributes to mitotic catastrophe and induction of cell death. Results also suggest that the decrease of telomeric-repeat binding factor 2 (TRF2 may be the earliest event in the ara-C-induced telomere shortening, induction of endoreduplication and chromosomal fragmentation leading to cell death.

  9. Fracture and Medium Modeling, by Analizing Hidraulic Fracturing Induced Microseismicity (United States)

    Gomez Alba, S.; Vargas Jiménez, C. A.


    Hydraulic fracturing is an essential technology for most unconventional hydrocarbon resources and many conventional ones as well. The primary limitation on the improvement and optimization of the fracturing process is the minimal access to observe the behavior of the fracture in the subsurface. Without direct observational evidence, hypothetical mechanisms must be assumed and then tested for their validity with indirect information such as wellbore measurements, indirect production and pressure behavior. One of the most important sources of information today is the relation made between micro seismic source mechanisms and fracture behavior. Hydraulic fractures induce some level of micro seismicity when the stress conditions in the Earth are altered by changes in stress during the operations. The result is the sudden movement between rock elements and the radiation of both compressional and shear energy in a seismic range that can be detected and recorded with sensitive receivers. The objective of this work is to provide reasonable information when applying inversion methods in order to estimate the vertical and horizontal spatial heterogeneities in medium and energy radiation distribution of microseisms while fracking operations. The method consist in record microseisms at a previous lineal array of stations (triaxial accelerometers) which are located close to the source coordinates and cover the area of study. The analysis clarify some ideas about what information can be gained from the micro seismic source data and according to the obtained results, what kind of comparisons and associations might be done to evaluate the fracking performance operation. Non uniformities in medium such as faults would be revealed by interpreted scattering coefficients. Fracture properties like distance, velocity and orientation would be also determined by analyzing energy radiation.

  10. Dynamic nature of cleavage bodies and their spatial relationship to DDX1 bodies, Cajal bodies, and gems. (United States)

    Li, Lei; Roy, Ken; Katyal, Sachin; Sun, Xuejun; Bléoo, Stacey; Godbout, Roseline


    DDX1 bodies, cleavage bodies, Cajal bodies (CBs), and gems are nuclear suborganelles that contain factors involved in RNA transcription and/or processing. Although all four nuclear bodies can exist as distinct entities, they often colocalize or overlap with each other. To better understand the relationship between these four nuclear bodies, we examined their spatial distribution as a function of the cell cycle. Here, we report that whereas DDX1 bodies, CBs and gems are present throughout interphase, CPSF-100-containing cleavage bodies are predominantly found during S and G2 phases, whereas CstF-64-containing cleavage bodies are primarily observed during S phase. All four nuclear bodies associate with each other during S phase, with cleavage bodies colocalizing with DDX1 bodies, and cleavage bodies/DDX1 bodies residing adjacent to gems and CBs. Although inhibitors of RNA transcription had no effect on DDX1 bodies or cleavage bodies, inhibitors of DNA replication resulted in loss of CstF-64-containing cleavage bodies. A striking effect on nuclear structures was observed with latrunculin B, an inhibitor of actin polymerization, resulting in the formation of needlelike nuclear spicules made up of CstF-64, CPSF-100, RNA, and RNA polymerase II. Our results suggest that cleavage body components are highly dynamic in nature.

  11. Dynamic Nature of Cleavage Bodies and Their Spatial Relationship to DDX1 Bodies, Cajal Bodies, and Gems (United States)

    Li, Lei; Roy, Ken; Katyal, Sachin; Sun, Xuejun; Bléoo, Stacey; Godbout, Roseline


    DDX1 bodies, cleavage bodies, Cajal bodies (CBs), and gems are nuclear suborganelles that contain factors involved in RNA transcription and/or processing. Although all four nuclear bodies can exist as distinct entities, they often colocalize or overlap with each other. To better understand the relationship between these four nuclear bodies, we examined their spatial distribution as a function of the cell cycle. Here, we report that whereas DDX1 bodies, CBs and gems are present throughout interphase, CPSF-100-containing cleavage bodies are predominantly found during S and G2 phases, whereas CstF-64-containing cleavage bodies are primarily observed during S phase. All four nuclear bodies associate with each other during S phase, with cleavage bodies colocalizing with DDX1 bodies, and cleavage bodies/DDX1 bodies residing adjacent to gems and CBs. Although inhibitors of RNA transcription had no effect on DDX1 bodies or cleavage bodies, inhibitors of DNA replication resulted in loss of CstF-64-containing cleavage bodies. A striking effect on nuclear structures was observed with latrunculin B, an inhibitor of actin polymerization, resulting in the formation of needlelike nuclear spicules made up of CstF-64, CPSF-100, RNA, and RNA polymerase II. Our results suggest that cleavage body components are highly dynamic in nature. PMID:16371507

  12. Extra Copper-mediated Enhancement of the DNA Cleavage Activity Supported with Wild-type Cu, Zn Superoxide Dismutase

    Institute of Scientific and Technical Information of China (English)

    ZHOU Ruo-Yu; JIANG Wei; ZHANG Li-Na; WANG Li; LIU Chang-Lin


    It is well known that the primary function of wild type Cu, Zn superoxide dismutase (holo SOD) is to catalyze the conversion of the superoxide anion to H2O2 and O2 as an antioxidant enzyme. However, the aberrant copper-mediated oxidation chemistry in the enzyme (including its mutation forms) that damages nucleic acids, proteins including itself and cell membrane has attracted extensive attention in the past decade. The present study examined the hydrogen peroxide-dependent DNA cleavage activity supported with the combinations between holo SOD and extra copper (holo SOD+nCu(Ⅱ)). The results indicate that the presence of extra copper can enhance the DNA cleavage activity and a cooperative effect between holo SOD and the extra Cu(Ⅱ) occurs in DNA cleavage. The relative activity and kinetic assay showed that the DNA cleavage activity of holo SOD+nCu(Ⅱ) was enhanced upon addition of extra Cu(Ⅱ). The favorable pH regions for the DNA cleavage were observed to be 3.6-5.6 and 9.0-10, suggesting the species responsible for the DNA cleavage are different in different pH regions. In addition,to obtain an insight into DNA cleavage pathways, the effect of free radical scavengers and inhibitors on the DNA cleavage activity was probed.

  13. Observation of Early Cleavage in Animal Development: A Simple Technique for Obtaining the Eggs of Rhabditis (Nematoda) (United States)

    Hinchliffe, J. R.


    Outlines the advantages of using the readily available eggs of the nematode Rhabditis in studying the early cleavage stages of animal development. Discusses the identification and life history of Rhabditis, how to culture and examine the organism, the cleavage stages and cell lineage, and sources of visual aids. (JR)

  14. Cleavage and survival of Xenopus embryos exposed to 8 T static magnetic fields in a rotating clinostat. (United States)

    Eguchi, Yawara; Ueno, Shoogo; Kaito, Chikara; Sekimizu, Kazuhisa; Shiokawa, Koichiro


    In this study, we examined cleavage and survival of fertilized Xenopus embryos exposed to 8 T static magnetic fields (SMFs). We investigated fertilized Xenopus embryos exposed to magnetic field either in static chamber or in a rotating culture system. Our results showed that the exposure to the strong magnetic field of 8 T changed the third cleavage furrow from the usual horizontal one to a perpendicular one; however, when the direction of gravity was randomized by exposing embryos to magnetic field in a rotating culture system, the third cleavage furrow were formed horizontally, a finding which suggests that the observed distortion of the third cleavage furrow in magnetism-exposed embryos was accomplished by altering gravity effects which were elicited by diamagnetic force due to high gradient magnetic field. Our results also showed that the exposure to the strong magnetic field did not damage survival. These results demonstrate that SMF and altering gravity cause distortion of the third cleavage furrow and show that effects of exposing cleavage embryos to magnetic field were transient and did not affect the post-cleavage development. We also showed that strong magnetic field is not hazardous to the cleavage and blastula-gastrula transition of developing embryonic cells.

  15. Prediction of Signal Peptide Cleavage Sites with Subsite-Coupled and Template Matching Fusion Algorithm. (United States)

    Zhang, Shao-Wu; Zhang, Ting-He; Zhang, Jun-Nan; Huang, Yufei


    Fast and effective prediction of signal peptides (SP) and their cleavage sites is of great importance in computational biology. The approaches developed to predict signal peptide can be roughly divided into machine learning based, and sliding windows based. In order to further increase the prediction accuracy and coverage of organism for SP cleavage sites, we propose a novel method for predicting SP cleavage sites called Signal-CTF that utilizes machine learning and sliding windows, and is designed for N-termial secretory proteins in a large variety of organisms including human, animal, plant, virus, bacteria, fungi and archaea. Signal-CTF consists of three distinct elements: (1) a subsite-coupled and regularization function with a scaled window of fixed width that selects a set of candidates of possible secretion-cleavable segment for a query secretory protein; (2) a sum fusion system that integrates the outcomes from aligning the cleavage site template sequence with each of the aforementioned candidates in a scaled window of fixed width to determine the best candidate cleavage sites for the query secretory protein; (3) a voting system that identifies the ultimate signal peptide cleavage site among all possible results derived from using scaled windows of different width. When compared with Signal-3L and SignalP 4.0 predictors, the prediction accuracy of Signal-CTF is 4-12 %, 10-25 % higher than that of Signal-3L for human, animal and eukaryote, and SignalP 4.0 for eukaryota, Gram-positive bacteria and Gram-negative bacteria, respectively. Comparing with PRED-SIGNAL and SignalP 4.0 predictors on the 32 archaea secretory proteins of used in Bagos's paper, the prediction accuracy of Signal-CTF is 12.5 %, 25 % higher than that of PRED-SIGNAL and SignalP 4.0, respectively. The predicting results of several long signal peptides show that the Signal-CTF can better predict cleavage sites for long signal peptides than SignalP, Phobius, Philius, SPOCTOPUS, Signal

  16. Thermodynamic Strategies for C-O Bond Formation and Cleavage via Tandem Catalysis. (United States)

    Lohr, Tracy L; Li, Zhi; Marks, Tobin J


    To reduce global reliance on fossil fuels, new renewable sources of energy that can be used with the current infrastructure are required. Biomass represents a major source of renewable carbon based fuel; however, the high oxygen content (∼40%) limits its use as a conventional fuel. To utilize biomass as an energy source, not only with current infrastructure, but for maximum energy return, the oxygen content must be reduced. One method to achieve this is to develop selective catalytic methods to cleave C-O bonds commonly found in biomass (aliphatic and aromatic ethers and esters) for the eventual removal of oxygen in the form of volatile H2O or carboxylic acids. Once selective methods of C-O cleavage are understood and perfected, application to processing real biomass feedstocks such as lignin can be undertaken. This Laboratory previously reported that recyclable "green" lanthanide triflates are excellent catalysts for C-O bond-forming hydroalkoxylation reactions. Based on the virtues of microscopic reversibility, the same lanthanide triflate catalyst should catalyze the reverse C-O cleavage process, retrohydroalkoxylation, to yield an alcohol and an alkene. However, ether C-O bond-forming (retrohydroalkoxylation) to form an alcohol and alkene is endothermic. Guided by quantum chemical analysis, our strategy is to couple endothermic, in tandem, ether C-O bond cleavage with exothermic alkene hydrogenation, thereby leveraging the combined catalytic cycles thermodynamically to form an overall energetically favorable C-O cleavage reaction. This Account reviews recent developments on thermodynamically leveraged tandem catalysis for ether and more recently, ester C-O bond cleavage undertaken at Northwestern University. First, the fundamentals of lanthanide-catalyzed hydroelementation are reviewed, with particular focus on ether C-O bond formation (hydroalkoxylation). Next, the reverse C-O cleavage/retrohydroalkoxylation processes enabled by tandem catalysis are

  17. Characterization of the prohormone complement in cattle using genomic libraries and cleavage prediction approaches

    Directory of Open Access Journals (Sweden)

    Rodriguez-Zas Sandra L


    Full Text Available Abstract Background Neuropeptides are cell to cell signalling molecules that regulate many critical biological processes including development, growth and reproduction. These peptides result from the complex processing of prohormone proteins, making their characterization both challenging and resource demanding. In fact, only 42 neuropeptide genes have been empirically confirmed in cattle. Neuropeptide research using high-throughput technologies such as microarray and mass spectrometry require accurate annotation of prohormone genes and products. However, the annotation and associated prediction efforts, when based solely on sequence homology to species with known neuropeptides, can be problematic. Results Complementary bioinformatic resources were integrated in the first survey of the cattle neuropeptide complement. Functional neuropeptide characterization was based on gene expression profiles from microarray experiments. Once a gene is identified, knowledge of the enzymatic processing allows determination of the final products. Prohormone cleavage sites were predicted using several complementary cleavage prediction models and validated against known cleavage sites in cattle and other species. Our bioinformatics approach identified 92 cattle prohormone genes, with 84 of these supported by expressed sequence tags. Notable findings included an absence of evidence for a cattle relaxin 1 gene and evidence for a cattle galanin-like peptide pseudogene. The prohormone processing predictions are likely accurate as the mammalian proprotein convertase enzymes, except for proprotein convertase subtilisin/kexin type 9, were also identified. Microarray analysis revealed the differential expression of 21 prohormone genes in the liver associated with nutritional status and 8 prohormone genes in the placentome of embryos generated using different reproductive techniques. The neuropeptide cleavage prediction models had an exceptional performance, correctly

  18. Molecular-dynamics Simulation-based Cohesive Zone Representation of Intergranular Fracture Processes in Aluminum (United States)

    Yamakov, Vesselin I.; Saether, Erik; Phillips, Dawn R.; Glaessgen, Edward H.


    A traction-displacement relationship that may be embedded into a cohesive zone model for microscale problems of intergranular fracture is extracted from atomistic molecular-dynamics simulations. A molecular-dynamics model for crack propagation under steady-state conditions is developed to analyze intergranular fracture along a flat 99 [1 1 0] symmetric tilt grain boundary in aluminum. Under hydrostatic tensile load, the simulation reveals asymmetric crack propagation in the two opposite directions along the grain boundary. In one direction, the crack propagates in a brittle manner by cleavage with very little or no dislocation emission, and in the other direction, the propagation is ductile through the mechanism of deformation twinning. This behavior is consistent with the Rice criterion for cleavage vs. dislocation blunting transition at the crack tip. The preference for twinning to dislocation slip is in agreement with the predictions of the Tadmor and Hai criterion. A comparison with finite element calculations shows that while the stress field around the brittle crack tip follows the expected elastic solution for the given boundary conditions of the model, the stress field around the twinning crack tip has a strong plastic contribution. Through the definition of a Cohesive-Zone-Volume-Element an atomistic analog to a continuum cohesive zone model element - the results from the molecular-dynamics simulation are recast to obtain an average continuum traction-displacement relationship to represent cohesive zone interaction along a characteristic length of the grain boundary interface for the cases of ductile and brittle decohesion. Keywords: Crack-tip plasticity; Cohesive zone model; Grain boundary decohesion; Intergranular fracture; Molecular-dynamics simulation

  19. Efficient and specific internal cleavage of a retroviral palindromic DNA sequence by tetrameric HIV-1 integrase.

    Directory of Open Access Journals (Sweden)

    Olivier Delelis

    Full Text Available BACKGROUND: HIV-1 integrase (IN catalyses the retroviral integration process, removing two nucleotides from each long terminal repeat and inserting the processed viral DNA into the target DNA. It is widely assumed that the strand transfer step has no sequence specificity. However, recently, it has been reported by several groups that integration sites display a preference for palindromic sequences, suggesting that a symmetry in the target DNA may stabilise the tetrameric organisation of IN in the synaptic complex. METHODOLOGY/PRINCIPAL FINDINGS: We assessed the ability of several palindrome-containing sequences to organise tetrameric IN and investigated the ability of IN to catalyse DNA cleavage at internal positions. Only one palindromic sequence was successfully cleaved by IN. Interestingly, this symmetrical sequence corresponded to the 2-LTR junction of retroviral DNA circles-a palindrome similar but not identical to the consensus sequence found at integration sites. This reaction depended strictly on the cognate retroviral sequence of IN and required a full-length wild-type IN. Furthermore, the oligomeric state of IN responsible for this cleavage differed from that involved in the 3'-processing reaction. Palindromic cleavage strictly required the tetrameric form, whereas 3'-processing was efficiently catalysed by a dimer. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that the restriction-like cleavage of palindromic sequences may be a general physiological activity of retroviral INs and that IN tetramerisation is strongly favoured by DNA symmetry, either at the target site for the concerted integration or when the DNA contains the 2-LTR junction in the case of the palindromic internal cleavage.

  20. Cleavage of galectin-3 by matrix metalloproteases induces angiogenesis in breast cancer (United States)

    Nangia-Makker, Pratima; Wang, Yi; Raz, Tirza; Tait, Larry; Balan, Vitaly; Hogan, Victor; Raz, Avraham


    Galectin-3 cleavage is related to progression of human breast and prostate cancer and is partly responsible for tumor growth, angiogenesis and apoptosis resistance in mouse models. A functional polymorphism in galectin-3 gene, determining its susceptibility to cleavage by matrix metalloproteinases (MMPs)-2/-9 is related to racial disparity in breast cancer incidence in Asian and Caucasian women. The purpose of our study is to evaluate (i) if cleavage of galectin-3 could be related to angiogenesis during the progression of human breast cancer, (ii) the role of cleaved galectin-3 in induction of angiogenesis and (iii) determination of the galectin-3 domain responsible for induction of angiogenic response. Galectin-3 null breast cancer cells BT-459 were transfected with either cleavable full-length galectin-3 or its fragmented peptides. Chemotaxis, chemoinvasion, heterotypic aggregation, epithelial-endothelial cell interactions and angiogenesis were compared to noncleavable galectin-3. BT-549-H64 cells harboring cleavable galectin-3 exhibited increased chemotaxis, invasion and interactions with endothelial cells resulting in angiogenesis and 3D morphogenesis compared to BT-549-P64 cells harboring noncleavable galectin-3. BT-549-H64 cells induced increased migration and phosphorylation of focal adhesion kinase in migrating endothelial cells. Endothelial cells cocultured with BT-549 cells transfected with galectin-3 peptides indicate that amino acids 1–62 and 33–250 stimulate migration and morphogenesis of endothelial cells. Immunohistochemical analysis of blood vessel density and galectin-3 cleavage in a breast cancer progression tissue array support the in vitro findings. We conclude that the cleavage of the N terminus of galectin-3 followed by its release in the tumor microenvironment in part leads to breast cancer angiogenesis and progression. PMID:20162566

  1. PROSPER: an integrated feature-based tool for predicting protease substrate cleavage sites.

    Directory of Open Access Journals (Sweden)

    Jiangning Song

    Full Text Available The ability to catalytically cleave protein substrates after synthesis is fundamental for all forms of life. Accordingly, site-specific proteolysis is one of the most important post-translational modifications. The key to understanding the physiological role of a protease is to identify its natural substrate(s. Knowledge of the substrate specificity of a protease can dramatically improve our ability to predict its target protein substrates, but this information must be utilized in an effective manner in order to efficiently identify protein substrates by in silico approaches. To address this problem, we present PROSPER, an integrated feature-based server for in silico identification of protease substrates and their cleavage sites for twenty-four different proteases. PROSPER utilizes established specificity information for these proteases (derived from the MEROPS database with a machine learning approach to predict protease cleavage sites by using different, but complementary sequence and structure characteristics. Features used by PROSPER include local amino acid sequence profile, predicted secondary structure, solvent accessibility and predicted native disorder. Thus, for proteases with known amino acid specificity, PROSPER provides a convenient, pre-prepared tool for use in identifying protein substrates for the enzymes. Systematic prediction analysis for the twenty-four proteases thus far included in the database revealed that the features we have included in the tool strongly improve performance in terms of cleavage site prediction, as evidenced by their contribution to performance improvement in terms of identifying known cleavage sites in substrates for these enzymes. In comparison with two state-of-the-art prediction tools, PoPS and SitePrediction, PROSPER achieves greater accuracy and coverage. To our knowledge, PROSPER is the first comprehensive server capable of predicting cleavage sites of multiple proteases within a single substrate

  2. Anaerobic DNA cleavage in red light by dicopper(II) complexes on disulphide bond activation

    Indian Academy of Sciences (India)

    Debojyoti Lahiri; Ritankar Majumdar; Ashis K Patra; Akhil R Chakravarty


    Binuclear complexes [Cu(-RSSR)]2 (1) and [M2(-PDS)(H2O)]2 (M = Cu(II), 2; Fe(II), 3), where H2RSSR is a reduced Schiff base derived from 2-(thioethyl)salicylaldimine having a disulphide moiety and H2PDS is derived from dimerization of D-penicillamine, have been prepared, structurally characterized, and their photo-induced DNA cleavage activity studied. The crystal structure of 1 shows the complex as a discrete binuclear species with each metal in a CuN2O2 square-planar geometry (Cu…Cu, 6.420 Å). The tetradentate RSSR2- acts as a bridging ligand. The sulphur atoms in the disulphide unit do not interact with the metal ions. Complexes 1-3 do not show any DNA cleavage activity in darkness. The copper(II) complexes exhibit chemical nuclease activity in the presence of 3-mercaptopropionic acid. Cleavage of supercoiled DNA has been observed in UV-A light of 365 nm for 1 and red light of 647.1 nm for both 1 and 2 in air. Mechanistic data reveal the involvement of the disulphide unit as photosensitizer generating hydroxyl radicals ($^{\\bullet}$OH) as the reactive species. Photo-induced DNA cleavage in red light seems to involve sulphide radicals in a type-I process and hydroxyl radicals. The dicopper(II) complexes show significant anaerobic photo-induced DNA cleavage activity in red light under argon following type-I pathway without involving any reactive oxygen species.

  3. Effect of Presenilin Mutations on APP Cleavage; Insights into the Pathogenesis of FAD. (United States)

    Li, Nuomin; Liu, Kefu; Qiu, Yunjie; Ren, Zehui; Dai, Rongji; Deng, Yulin; Qing, Hong


    Alzheimer disease (AD) is characterized by progressive memory loss, reduction in cognitive functions, and damage to the brain. The β-amyloid precursor protein can be sequentially cleaved by β- secretase and γ-secretase. Mutations in the presenilin1(PS1) are the most common cause of Familial Alzheimer's disease (FAD). PS1 mutations can alter the activity of γ-secretase on the cleavage of the β-amyloid precursor protein, causing increased Aβ production. Previous studies show that the βAPP-C-terminal fragment is first cleaved by β-scretase, primarily generating long fragments of Aβ48 and Aβ49, followed by the stepwise cleavage of every three amino acid residues at the C terminus, resulting in Aβ48-, 45-, 42 line and Aβ49-, 46-, 43-, 40 line. Here, we used LC-MS/MS to analyze unique peptides IAT, VVIA, ITL, TVI, IVI through sequential cleavage, combined with ELISA to test the level of Aβ42 and Aβ40 for validation. The results show that most FAD mutant PS1 can alter the level of Aβ42 and Aβ40 monitored by the Aβ42/Aβ40 ratio. Among them, six mutants (I143T, H163P, S170F, Q223R, M233V, and G384A) affect the Aβ42/40 ratio through both Aβ49-40 and Aβ48-38 lines; L166P through decreasing the Aβ49-40 line, six mutants (I143V, M146V, G217A, E280A, L381V, and L392V) through increasing the Aβ48-42 line. More importantly, we found some mutations can affect the γ-secretase cleavage preference of α-CTF and β-CTF. In conclusion, we found that the FAD PS1 mutations mainly increase the generation of Aβ42 by decreasing the cleavage of Aβ42-Aβ38 and Aβ43-Aβ40.

  4. Endoproteolytic cleavage of TUG protein regulates GLUT4 glucose transporter translocation. (United States)

    Bogan, Jonathan S; Rubin, Bradley R; Yu, Chenfei; Löffler, Michael G; Orme, Charisse M; Belman, Jonathan P; McNally, Leah J; Hao, Mingming; Cresswell, James A


    To promote glucose uptake into fat and muscle cells, insulin causes the translocation of GLUT4 glucose transporters from intracellular vesicles to the cell surface. Previous data support a model in which TUG traps GLUT4-containing vesicles and tethers them intracellularly in unstimulated cells and in which insulin mobilizes this pool of vesicles by releasing this tether. Here we show that TUG undergoes site-specific endoproteolytic cleavage, which separates a GLUT4-binding, N-terminal region of TUG from a C-terminal region previously suggested to bind an intracellular anchor. Cleavage is accelerated by insulin stimulation in 3T3-L1 adipocytes and is highly dependent upon adipocyte differentiation. The N-terminal TUG cleavage product has properties of a novel 18-kDa ubiquitin-like modifier, which we call TUGUL. The C-terminal product is observed at the expected size of 42 kDa and also as a 54-kDa form that is released from membranes into the cytosol. In transfected cells, intact TUG links GLUT4 to PIST and also binds Golgin-160 through its C-terminal region. PIST is an effector of TC10α, a GTPase previously shown to transmit an insulin signal required for GLUT4 translocation, and we show using RNAi that TC10α is required for TUG proteolytic processing. Finally, we demonstrate that a cleavage-resistant form of TUG does not support highly insulin-responsive GLUT4 translocation or glucose uptake in 3T3-L1 adipocytes. Together with previous results, these data support a model whereby insulin stimulates TUG cleavage to liberate GLUT4 storage vesicles from the Golgi matrix, which promotes GLUT4 translocation to the cell surface and enhances glucose uptake.

  5. Discrete modeling of hydraulic fracturing processes in a complex pre-existing fracture network (United States)

    Kim, K.; Rutqvist, J.; Nakagawa, S.; Houseworth, J. E.; Birkholzer, J. T.


    Hydraulic fracturing and stimulation of fracture networks are widely used by the energy industry (e.g., shale gas extraction, enhanced geothermal systems) to increase permeability of geological formations. Numerous analytical and numerical models have been developed to help understand and predict the behavior of hydraulically induced fractures. However, many existing models assume simple fracturing scenarios with highly idealized fracture geometries (e.g., propagation of a single fracture with assumed shapes in a homogeneous medium). Modeling hydraulic fracture propagation in the presence of natural fractures and homogeneities can be very challenging because of the complex interactions between fluid, rock matrix, and rock interfaces, as well as the interactions between propagating fractures and pre-existing natural fractures. In this study, the TOUGH-RBSN code for coupled hydro-mechanical modeling is utilized to simulate hydraulic fracture propagation and its interaction with pre-existing fracture networks. The simulation tool combines TOUGH2, a simulator of subsurface multiphase flow and mass transport based on the finite volume approach, with the implementation of a lattice modeling approach for geomechanical and fracture-damage behavior, named Rigid-Body-Spring Network (RBSN). The discrete fracture network (DFN) approach is facilitated in the Voronoi discretization via a fully automated modeling procedure. The numerical program is verified through a simple simulation for single fracture propagation, in which the resulting fracture geometry is compared to an analytical solution for given fracture length and aperture. Subsequently, predictive simulations are conducted for planned laboratory experiments using rock-analogue (soda-lime glass) samples containing a designed, pre-existing fracture network. The results of a preliminary simulation demonstrate selective fracturing and fluid infiltration along the pre-existing fractures, with additional fracturing in part

  6. Serine-selective aerobic cleavage of peptides and a protein using a water-soluble copper-organoradical conjugate. (United States)

    Seki, Yohei; Tanabe, Kana; Sasaki, Daisuke; Sohma, Youhei; Oisaki, Kounosuke; Kanai, Motomu


    The site-specific cleavage of peptide bonds is an important chemical modification of biologically relevant macromolecules. The reaction is not only used for routine structural determination of peptides, but is also a potential artificial modulator of protein function. Realizing the substrate scope beyond the conventional chemical or enzymatic cleavage of peptide bonds is, however, a formidable challenge. Here we report a serine-selective peptide-cleavage protocol that proceeds at room temperature and near neutral pH value, through mild aerobic oxidation promoted by a water-soluble copper-organoradical conjugate. The method is applicable to the site-selective cleavage of polypeptides that possess various functional groups. Peptides comprising D-amino acids or sensitive disulfide pairs are competent substrates. The system is extendable to the site-selective cleavage of a native protein, ubiquitin, which comprises more than 70 amino acid residues.

  7. Plain film analysis of acetabular fracture

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chang Soo; Han, Sang Suk; Yoon, Eu Giene; Cha, Seong Sook; Eun, Tchoong Kie; Chung, Duck Hwan [Inje Medical College Paik Hospital, Pusan (Korea, Republic of)


    Acetabular fracture can result in severe limitation of the motion of the hip joint, which supports total weight of human body. Because of different methods of surgical approach according to fracture type, precise interpretation of X-ray films of acetabular fracture is required. We reviewed 38 cases of simple X-ray films showing acetabular fracture. The results were as follows: 1. Almost 60% of the cases-were in their 2nd and 3rd decades. 2. Twenty cases were male, and 18 cases were female. 3. The most common cause of the injury was traffic accident (33 cases, 86.8%), followed by fall down (4 cases, 10.5%), and slip down (1 case, 2.7%). 4. Elementary fractures were 21 cases (55.3%), and associated fractures were 17 cases (44.7%). 5. Among elementary fractures, posterior wall fractures were 9 cases (23.7%), followed by anterior column fractures (8 cases, 21.1%), anterior wall fractures (4 cases, 10.5%). 6. Among associated fractures, T-shaped fractures were 8 cases (21.1%), followed by both column fractures (6 cases, 15.8%), anterior and hemitransverse fractures (3 cases, 7.8%). 7. Other pelvic bone fractures associated with the acetabular fracture were as follows: fractures of contralateral pubic rami (6 cases, 15.8%) contralateral iliac bone (1 case, 2.6%) and ipsilateral iliac bone (1 case, 2.6%). 8. Injuries of other organs adjacent to the acetabulum were as follows: rupture of the bladder (3 cases, 7.9%), urethra (2 cases, 5.3%) and uterus (1 cases, 2.6%)

  8. Fracture mechanics of PGX graphite

    Energy Technology Data Exchange (ETDEWEB)

    Ho, F.H.; Vollman, R.E.; Cull, A.D.


    Fracture mechanics tests were performed on grade PGX graphite. A compact tension specimen configuration which yields consistent values of the opening mode critical stress intensity factor K/sub IC/, was designed. For the calculation of the fracture toughness and crack growth rate the concept of the effective crack length is used. It corresponds to the crack length of a machined notched specimen with the same compliance. Fracture toughness testing was performed in two environments, air and helium, both at room temperature. The critical stress intensity factor, K/sub IC/, is calculated based on the maximum load and the effective crack length. The fatigue crack growth test was performed in air only. A break-in period was observed for the machined notch to develop into a naturally occurring crack path. Half of the fatigue life was spent in this period.

  9. [Fractures of the elbow joint]. (United States)

    Nowak, T E; Dietz, S O; Burkhart, K J; Müller, L P; Rommens, P M


    Fractures around the elbow joint comprise fractures of the distal humerus, the radial head, the olecranon and the coronoid process. Combined lesions are particularly demanding for the surgeon. Accurate knowledge of the anatomy and of the biomechanics is an essential requirement for a specific diagnosis and therapy. A stable and painless movable elbow joint is essential for most of the activities of daily living. Risk factors for the development of posttraumatic elbow joint arthrosis are non-anatomically reconstructed joint surfaces, axial malalignment of the joint axis and untreated concomitant injuries. Modern angular stable and anatomically preshaped implants facilitate a biomechanically adequate osteosynthesis and avoid or decrease functional impairment. In consideration of an increasing number of osteoporotic elbow joint fractures, endoprosthetic replacement has gained significance.

  10. Fracture toughness evaluation of 20MnMoNi55 pressure vessel steel in the ductile to brittle transition regime: Experiment & numerical simulations (United States)

    Gopalan, Avinash; Samal, M. K.; Chakravartty, J. K.


    In this work, fracture behaviour of 20MnMoNi55 reactor pressure vessel (RPV) steel in the ductile to brittle transition regime (DBTT) is characterised. Compact tension (CT) and single edged notched bend (SENB) specimens of two different sizes were tested in the DBTT regime. Reference temperature 'T0' was evaluated according to the ASTM E1921 standard. The effect of size and geometry on the T0 was studied and T0 was found to be lower for SENB geometry. In order to understand the fracture behaviour numerically, finite element (FE) simulations were performed using Beremin's model for cleavage and Rousselier's model for ductile failure mechanisms. The simulated fracture behaviour was found to be in good agreement with the experiment.

  11. Dynamic fracture of heterogeneous materials

    Energy Technology Data Exchange (ETDEWEB)

    Stout, M.G.; Liu, C.; Addessio, F.L.; Williams, T.O.; Bennett, J.G.; Haberman, K.S.; Asay, B.W.


    This is the final report of a one-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The objective of this project was to investigate the fundamental aspects of the process of dynamic fracture propagation in heterogeneous materials. The work focused on three important, but poorly understood, aspects of dynamic fracture for materials with a heterogeneous microstructure. These were: the appropriateness of using a single-parameter asymptotic analysis to describe dynamic crack-tip deformation fields, the temperature rises at the tip and on the flanks of a running crack, and the constitutive modeling of damage initiation and accumulation.

  12. Trapezoid fracture caused by assault

    Directory of Open Access Journals (Sweden)

    Malshikare V


    Full Text Available In this report we describe an open fracture of trapezoid and break in anterior cortex of capitate due to assault in a young adult male. Direct impact force of a sharp object to the first web space caused the above fractures. Open reduction and internal fixation of the trapezoid was carried out using Kirschner wires. Cut extensor tendons, extensor retaniculum, capsule, adductor pollicis muscle, first dorsal interosseous muscle, soft tissue and overlying skin were sutured primarily. Three months after the operation the patient has made a complete recovery. There is no similar case reported in the literature.

  13. Hydrogen fracture toughness tester completion

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, Michael J. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)


    The Hydrogen Fracture Toughness Tester (HFTT) is a mechanical testing machine designed for conducting fracture mechanics tests on materials in high-pressure hydrogen gas. The tester is needed for evaluating the effects of hydrogen on the cracking properties of tritium reservoir materials. It consists of an Instron Model 8862 Electromechanical Test Frame; an Autoclave Engineering Pressure Vessel, an Electric Potential Drop Crack Length Measurement System, associated computer control and data acquisition systems, and a high-pressure hydrogen gas manifold and handling system.

  14. [Vertical fractures: apropos of 2 clinical cases]. (United States)

    Félix Mañes Ferrer, J; Micò Muñoz, P; Sánchez Cortés, J L; Paricio Martín, J J; Miñana Laliga, R


    The aim of the study is to present a clinical review of the vertical root fractures. Two clinical cases are presented to demonstrates the criteria for obtaining a correct diagnosis of vertical root fractures.

  15. Subclinical Thyroid Dysfunction and Fracture Risk

    DEFF Research Database (Denmark)

    Blum, Manuel R; Bauer, Douglas C; Collet, Tinh-Hai;


    . Levels of thyroid function were defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mIU/L), subclinical hyperthyroidism (TSH subclinical hypothyroidism (TSH ≥4.50-19.99 mIU/L) with normal thyroxine concentrations. MAIN OUTCOME AND MEASURES: The primary outcome was hip...... fracture. Any fractures, nonspine fractures, and clinical spine fractures were secondary outcomes. RESULTS: Among 70,298 participants, 4092 (5.8%) had subclinical hypothyroidism and 2219 (3.2%) had subclinical hyperthyroidism. During 762,401 person-years of follow-up, hip fracture occurred in 2975...... participants (4.6%; 12 studies), any fracture in 2528 participants (9.0%; 8 studies), nonspine fracture in 2018 participants (8.4%; 8 studies), and spine fracture in 296 participants (1.3%; 6 studies). In age- and sex-adjusted analyses, the hazard ratio (HR) for subclinical hyperthyroidism vs euthyroidism...

  16. Toe and Metatarsal Fractures (Broken Toes) (United States)

    ... rest is the only treatment needed to promote healing of a stress or traumatic fracture of a metatarsal bone. Avoid the offending activity. Because stress fractures result from repetitive stress, it ...


    Institute of Scientific and Technical Information of China (English)

    Li-yang Dai


    Objective To review imaging use in the diagnosis ofthoracolumbar burst fractures and to determine the diagnostic value of different imaging methods.Methods One hundred and fourteen patients with 120 thoracolumbar burst fractures were retrospectively reviewed. Plain radiographs were available in all cases; CT scans and MRI were obtained in 96 and 74 cases, respectively.Results A total of 27 burst fractures were misdiagnosed as other types of fractures on radiographs alone, and accounted for 22.5% of all fractures. The results indicated that plain radiographs often fail to delineate the pathological features of thoracolumbar burst fractures, leading to delay in diagnosis.Conclusion In regard to thoracolumbar injury diagnosis, burst fractures should be differentiated from compression fractures. CT should be routinely indicated and MRI examination, when necessary, may be simultaneously considered.

  18. Topological impact of constrained fracture growth

    Directory of Open Access Journals (Sweden)

    Sigmund Mongstad Hope


    Full Text Available The topology of two discrete fracture network models is compared to investigate the impact of constrained fracture growth. In the Poissonian discrete fracture network model the fractures are assigned length, position and orientation independent of all other fractures, while in the mechanical discrete fracture network model the fractures grow and the growth can be limited by the presence of other fractures. The topology is found to be impacted by both the choice of model, as well as the choice of rules for the mechanical model. A significant difference is the degree mixing. In two dimensions the Poissonian model results in assortative networks, while the mechanical model results in disassortative networks. In three dimensions both models produce disassortative networks, but the disassortative mixing is strongest for the mechanical model.

  19. Surgical treatment for complicated acetabular fractures

    Institute of Scientific and Technical Information of China (English)

    Ning An; Yang Yanmin


    Objective: To sum up the surgical approaches and clinical outcome of complicated acetabular fractures. Methods: 17 patients with complicated acetabular fractures (including 4 cases of transverse with posterior wall fractures, 7 cases of posterior column and wall fractures, 4 cases of anterior and posterior columns fractures, 1 cases of T-type fracture and 1 cases of anterior column with posterior hemitransverse fractures) underwent open reduction and internal fixation with screws and plates by Kocher-Langenbeck (8 cases), ilio-inguinal (2 cases), extended iliofemoral (4 cases) or ilio-inguinal combined with K-L approaches (3 cases). Results: 12 patients with anatomical reduction, 4 patients with satisfactory reduction and 1 patient with non-satisfactory reduction. 15 out of 17 cases were followed up for 6 months to 5 years, and the excellent and good rate was 70.5%. Conclusion: Surgical treatment for complicated acetabular fractures can get a satisfactory reduction and a good clinical outcome.

  20. Zoledronic acid and clinical fractures and mortality after hip fracture

    DEFF Research Database (Denmark)

    Lyles, Kenneth W; Colón-Emeric, Cathleen S; Magaziner, Jay S;


    receiving zoledronic acid were pyrexia, myalgia, and bone and musculoskeletal pain. No cases of osteonecrosis of the jaw were reported, and no adverse effects on the healing of fractures were noted. The rates of renal and cardiovascular adverse events, including atrial fibrillation and stroke, were similar...

  1. Fracture Rates and Fracture Sites in Patients With Osteogenesis Imperfecta

    DEFF Research Database (Denmark)

    Folkestad, Lars; Hald, Jannie Dahl; Ersbøll, Annette Kjær;


    Osteogenesis imperfecta (OI) is a hereditary, clinically heterogeneous, connective tissue disorder. The population prevalence of OI in Denmark is 10.6 in 100,000. A hallmark of the disease is frequent fractures that are often precipitated by minimal trauma. The aim of the current study...

  2. Quantifying Fracture Heterogeneity in Different Domains of Folded Carbonate Rocks to Improve Fractured Reservoir Analog Fluid Flow Models

    NARCIS (Netherlands)

    Bisdom, K.; Bertotti, G.; Gauthier, B.D.M.; Hardebol, N.J.


    Fluid flow in carbonate reservoirs is largely controlled by multiscale fracture networks. Significant variations of fracture network porosity and permeability are caused by the 3D heterogeneity of the fracture network characteristics, such as intensity, orientation and size. Characterizing fracture

  3. Pedicular stress fracture in the lumbar spine

    Energy Technology Data Exchange (ETDEWEB)

    Chong, V.F.H.; Htoo, M.M. [Singapore General Hospital, Singapore, (Singapore). Department of Diagnostic Radiology


    Spondylolisthesis with or without spondylolysis is common in the lumbar spine. Associated fracture in the pedicle (`pediculolysis`) is unusual. The margins of pedicular stress fractures, like spondylolysis, usually appear sclerotic. A patient with a pedicular stress fracture with minimal marginal sclerosis suggesting an injury of recent onset is presented here. There was associated bilateral spondylolysis. The findings in this patient suggest that established pediculolysis probably represents a stress fracture that has failed to heal. (authors). 10 refs., 2 figs.

  4. Interpretation of stress damage on fracture conductivity

    Energy Technology Data Exchange (ETDEWEB)

    Berumen, Sergio; Tiab, Djebbar [PEMEX E and P and The University of Oklahoma, School of Petroleum and Geological Engineering, Norman, OK (United States)


    This paper focuses on the investigation of pressure responses in a well producing through a composite system of a stress-sensitive vertical symmetric or asymmetric fracture interacting with a stress-sensitive permeable-porous medium. Results of this investigation demonstrate that when the fracture conductivity is stress dependent, the use of conventional techniques to evaluate fractured wells may lead to incorrect estimates of the fracture-formation properties. For finite conductivity fractures, the stress effects in the formation have a negligible influence on the absolute value of the slope that defines the pseudo-bilinear flow regime. During this flow regime only the pressure sensitivity in the fracture and the fracture conductivity govern this flow period. For cases that involve highly conductive fractures, it was found that the slope of 0.5 which defines the linear flow regime is not influenced by the stress effect of the fracture and formation. However, stress in highly conductive fractures has a measurable influence in the change of conductivity. The occurrence of the stress damage in finite and infinite conductivity fractures is due to the partial closure fracture or partial choke fracture effect and can be anticipated in terms of pressure or time level by using the equations provided in this work. The results derived from this research have a major impact in improving the analysis of fractured wells pressure responses, as well as in forecasting of fracture closure occurrence and in programming stimulation operations in fractured wells. An example with synthetic data is presented to illustrate these new findings

  5. Subtrochanteric femur fracture after removal of screws for femoral neck fracture in a child. (United States)

    Song, Kwang Soon; Lee, Si Wook


    Displaced femoral neck fractures are rare in children and are associated with a high rate of complications. Subtrochanteric fractures after cannulated screw fixation of femoral neck fractures in adults are well recognized, and there are several reports on the topic. However, there are no reports on complications related to hardware or subtrochanteric fractures after removal of the screws in the treatment of femoral neck fractures in children. Here we report the case of a 10-year-old boy who sustained a subtrochanteric fracture after the screw removal and healing that followed a femoral neck fracture.

  6. Subtrochanteric fractures in bisphosphonate-naive patients

    DEFF Research Database (Denmark)

    Adachi, Jonathan D; Lyles, Kenneth; Boonen, Steven


    Our purpose was to characterize the risks of osteoporosis-related subtrochanteric fractures in bisphosphonate-naive individuals. Baseline characteristics of patients enrolled in the HORIZON-Recurrent Fracture Trial with a study-qualifying hip fracture were examined, comparing those who sustained ...

  7. 49 CFR 195.111 - Fracture propagation. (United States)


    ... 49 Transportation 3 2010-10-01 2010-10-01 false Fracture propagation. 195.111 Section 195.111... PIPELINE Design Requirements § 195.111 Fracture propagation. A carbon dioxide pipeline system must be designed to mitigate the effects of fracture propagation....

  8. Atypical subtrochanteric and diaphyseal femoral fractures

    DEFF Research Database (Denmark)

    Shane, Elizabeth; Burr, David; Abrahamsen, Bo;


    that distinguish AFFs from ordinary osteoporotic femoral diaphyseal fractures and to provide guidance on the importance of their transverse orientation. The requirement that fractures be noncomminuted was relaxed to include minimal comminution. The periosteal stress reaction at the fracture site was changed from...

  9. Locking plates in proximal humerus fractures. (United States)

    Strohm, P C; Helwig, P; Konrad, G; Südkamp, N P


    It is well known that proximal humerus fractures are among the three most frequent fracture types. Epidemiological invetsigations show that in people elder than 60 years the fracture of the proximal humerus is more frequent than fractures of the hip region (17). Over the last decades several techniques have been applied for treatment of proximal humerus fractures. Widely accepted is the initiation of a conservative treatment regimen for undisplaced fractures, however, the standard treatment for displaced fractures, especially three and four part fractures, is still the center of scientific debate. Many different implants have been tested and investigated, thus demonstrating lack of sufficient results. Over the last years the development of angle stable, locking implants started and clinical studies demonstrated encouraging results. In our clinic the locking proximal humerus plate and the PHILOS plate advanced to the implant of choice for treatment of displaced proximal humerus fractures. There are still cases of implant failure and humerus head necrosis, but most of these complications were caused by the fracture type and not an implant specific problem. However the overall results with these new implants are encouraging. Key words: locking plates, proximal humerus fracture, humerus, humerus fracture, PHILOS, PHP.

  10. Fractures in infants and toddlers with rickets

    Energy Technology Data Exchange (ETDEWEB)

    Chapman, Teresa; Done, Stephen [Seattle Children' s Hospital, Department of Radiology, Seattle, WA (United States); Sugar, Naomi; Feldman, Kenneth [Seattle Children' s Hospital, Children' s Protection Program, Seattle, WA (United States); Marasigan, Joanne; Wambold, Nicolle [University of Washington, College of Arts and Sciences, Seattle, WA (United States)


    Rickets affects young infants and toddlers. However, there is a paucity of literature regarding the types of fractures that occur in rachitic patients. To evaluate the age of patients at which radiographically evident rickets occurs, and to characterize the age incidence and fractures that are observed in infants and toddlers with radiographically evident rickets. A retrospective study of children younger than 24 months was performed. Clinical data and radiographs were reviewed. Radiographs obtained within 1 month of the diagnosis were evaluated for the presence or absence of osteopenia, presence or absence of fraying-cupping, and presence and characterization of fractures. After exclusion criteria were applied, 45 children were included in the study. Children with rickets evident by radiograph were in the age range of 2-24 months. Fractures were present in 17.5% of the study group, exclusively in mobile infants and toddlers. Fracture types included transverse long bone fractures, anterior and anterior-lateral rib fractures, and metaphyseal fractures. All fractures occurred exclusively in patients with severe, overtly evident rickets. Fractures occur in older infants and toddlers with overt rickets and can be seen by radiograph. Fractures do not resemble high-risk non-accidental trauma fractures. (orig.)

  11. Phalangeal bone mineral density predicts incident fractures

    DEFF Research Database (Denmark)

    Friis-Holmberg, Teresa; Brixen, Kim; Rubin, Katrine Hass;


    This prospective study investigates the use of phalangeal bone mineral density (BMD) in predicting fractures in a cohort (15,542) who underwent a BMD scan. In both women and men, a decrease in BMD was associated with an increased risk of fracture when adjusted for age and prevalent fractures...

  12. Functional outcome after a spinal fracture

    NARCIS (Netherlands)

    Post, Richard Bernardus


    This thesis takes a closer look at the functional outcome after a spinal fracture. An introduction to different aspects regarding spinal fractures is presented in Chapter 1. The incidence of traumatic thoracolumbar spinal fractures without neurological deficit in the Netherlands is approximately 1.2

  13. Identification and characterization of a cleavage site in the proteolysis of orf virus 086 protein

    Directory of Open Access Journals (Sweden)

    Xiaoping eWang


    Full Text Available The ORF virus (ORFV is among the parapoxvirus genus of the poxviridae family, but little is known about the proteolytic pathways of ORFV encoding proteins. By contrast, the proteolysis mechanism of the vaccinia virus has been extensively explored. Vaccinia virus core protein P4a undergoes a proteolytic process that takes place at a conserved cleavage site Ala-Gly-X (where X is any amino acid and participates in virus assembly. Bioinformatics analysis revealed that an ORFV encoding protein, ORFV086, has a similar structure to the Vaccinia virus P4a core protein. In this study, we focus on the kinetic analysis and proteolysis mechanism of ORFV086. We found, via kinetic analysis, that ORFV086 is a late gene that starts to express at 8 hours post infection at mRNA level and 12 to 24 hours post infection at the protein level. The ORFV086 precursor and a 21kDa fragment can be observed in mature ORFV virions. The same bands were detected at only 3 hours post infection, suggesting that both the ORFV086 precursor and the 21kDa fragment are viral structural proteins. ORFV086 was cleaved from 12 to 24 hours post infection. The cleavage took place at different sites,resulting in seven bands with differing molecular weights. Sequence alignment revealed that five putative cleavage sites were predicted at C-terminal and internal regions of ORFV086. To investigate whether those cleavage sites are involved in proteolytic processing, full length and several deletion mutant ORFV086 recombinant proteins were expressed and probed. The GGS site that produced a 21kDa cleavage fragment was confirmed by identification of N/C-terminal FLAG epitope recombinant proteins, site-directed mutagenesis and Pulse-chase analysis. Interestingly, chase results demonstrated that, at late times, ORFV086 is partially cleaved. Taken together, we concluded that GGS is a cleavage site in ORFV086 and produces a 21kDa fragment post infection. Both ORFV086 precursor and the 21kDa fragment

  14. Sport-related maxillofacial fractures

    NARCIS (Netherlands)

    Ruslin, M.; Boffano, P.; ten Brincke, Y.J.D.; Forouzanfar, T.; Brand, H.S.


    Sports and exercise are important causes of maxillofacial injuries. Different types of sports might differ in frequency and type of fractures. The aim of the present study was to explore the possible relation between the types of sport practiced and the frequency and nature of the facial bone fractu

  15. Fractures of the proximal humerus

    DEFF Research Database (Denmark)

    Brorson, Stig


    Fractures of the proximal humerus have been diagnosed and managed since the earliest known surgical texts. For more than four millennia the preferred treatment was forceful traction, closed reduction, and immobilization with linen soaked in combinations of oil, honey, alum, wine, or cerate...

  16. Hydraulic fracturing system and method

    Energy Technology Data Exchange (ETDEWEB)

    Ciezobka, Jordan; Salehi, Iraj


    A hydraulic fracturing system and method for enhancing effective permeability of earth formations to increase hydrocarbon production, enhance operation efficiency by reducing fluid entry friction due to tortuosity and perforation, and to open perforations that are either unopened or not effective using traditional techniques, by varying a pump rate and/or a flow rate to a wellbore.

  17. Social inequality and hip fracture

    DEFF Research Database (Denmark)

    Harvey, N. C.; Hansen, L.; Judge, A.


    Social inequality appears to be increasing in many countries. We explored whether risk of hip fracture was associated with markers of inequality and whether these relationships changed with time, using data from Danish Health Registries. Methods: All patients 60 years or older with a primary hip...

  18. Subtrochanteric fractures in bisphosphonate-naive patients: results from the HORIZON-recurrent fracture trial. (United States)

    Adachi, Jonathan D; Lyles, Kenneth; Boonen, Steven; Colón-Emeric, Cathleen; Hyldstrup, Lars; Nordsletten, Lars; Pieper, Carl; Recknor, Chris; Su, Guoqin; Bucci-Rechtweg, Christina; Magaziner, Jay


    Our purpose was to characterize the risks of osteoporosis-related subtrochanteric fractures in bisphosphonate-naive individuals. Baseline characteristics of patients enrolled in the HORIZON-Recurrent Fracture Trial with a study-qualifying hip fracture were examined, comparing those who sustained incident subtrochanteric fractures with those sustaining other hip fractures. Subjects were bisphosphonate-naive or had a bisphosphonate washout period of 6-24 months and subsequently received an annual infusion of zoledronic acid 5 mg or placebo after low-trauma hip-fracture repair. In total, 2,127 men and women were included. Of the qualifying hip fractures, 5.2% were subtrochanteric, 54.8% femoral neck, 33.0% intertrochanteric, and 7.1% other (generally complex fractures of mixed type). Significant baseline (pre-hip fracture) differences were seen between index hip-fracture types, with the percentage of patients with extreme mobility problems being twofold higher in patients with index subtrochanteric fracture (9.9%) compared to other patients. The distribution of hip-fracture types was similar between the treatment groups at baseline. No patients with index subtrochanteric fractures and six patients with other qualifying hip fractures reported prior bisphosphonate use. Only one further subtrochanteric fracture occurred in each treatment group over an average 2-year patient follow-up. Subtrochanteric fractures are not uncommon in bisphosphonate-naive patients. Extreme difficulties with mobility may be a unique risk factor predisposing to development of incident subtrochanteric fractures rather than other types of hip fracture. In patients with recent hip fracture who received zoledronic acid therapy, the incidence of new subtrochanteric fractures was too small to draw any meaningful conclusions.

  19. Subtrochanteric Fractures in Bisphosphonate-Naive Patients: Results from the HORIZON-Recurrent Fracture Trial



    Our purpose was to characterize the risks of osteoporosis-related subtrochanteric fractures in bisphosphonate-naive individuals. Baseline characteristics of patients enrolled in the HORIZON-Recurrent Fracture Trial with a study-qualifying hip fracture were examined, comparing those who sustained incident subtrochanteric fractures with those sustaining other hip fractures. Subjects were bisphosphonate-naive or had a bisphosphonate washout period of 6–24 months and subsequently received an annu...

  20. Low-trauma fractures indicate increased risk of hip fracture in frail older people. (United States)

    Chen, Jian Sheng; Cameron, Ian D; Simpson, Judy M; Seibel, Markus J; March, Lyn M; Cumming, Robert G; Lord, Stephen R; Sambrook, Philip N


    This study aims to investigate the risk of subsequent fractures after low-trauma fracture in frail older people. A total of 1412 elderly residents (mean age 86.2 years, SD 7.0 years, female 77%) were recruited from aged care facilities in Australia. Residents were assessed and then followed for any fracture for 2 years and hip fractures for at least 5 years. Residents with and without a newly acquired fracture in the first 2 years were compared for risk of subsequent hip fracture. Residents with a nonhip fracture in the first 2 years had an increased risk of subsequent hip fracture for about 2.5 years, whereas those with a hip fracture had a similar risk over the whole period compared with those with no fracture. During these 2.5 years, 60, 28, and 6 subsequent hip fractures occurred in the nonfracture group (n = 953), the nonhip fracture group (n = 194), and the hip fracture group (n = 101), respectively, resulting in the probability of subsequent hip fracture of 8.0%, 19.9%, and 10.4%, respectively. Compared with the nonfracture group, the hazard ratio (HR) was 2.82 [95% confidence interval (CI) 1.73-4.59; p < .001] for the nonhip fracture group and 1.48 (95% CI 0.63-3.49, p = .37) for the hip fracture group after adjusting for age, sex, residence type, calcaneal broadband ultrasound attenuation, fracture history, weight, lower leg length, immobility, cognitive function, and medications. Frail institutionalized older people with newly acquired fractures are at increased risk of subsequent hip fracture for the next few years. Accordingly, despite their advanced age, they are a high-priority target group to investigate interventions that might reduce the risk of hip fracture.

  1. Room-temperature fracture in V-(4-5)Cr-(4-5)Ti tensile specimens irradiated in Fusion-1 BOR-60 experiment

    Energy Technology Data Exchange (ETDEWEB)

    Gazda, J.; Meshii, M. [Northwestern Univ., Evanston, IL (United States); Tsai, H. [Argonne National Lab., IL (United States)


    Specimens of V-(4-5)Cr-(4-5)Ti alloys were irradiated to {approx}18 dpa at 320 C in the Fusion-1 capsule inserted into the BOR-60 reactor. Tensile tests at 23 C indicated dramatic yield strength increase (>300%), lack of work hardening, and minimal (<1%) total elongations. SEM analysis of fracture and side surfaces were conducted to determine reduction in are and the mode of fracture. The reduction of area was negligible. All but one specimen failed by a combination of ductile shear deformation and cleavage crack growth. Transgranular cleavage cracks were initiated by stress concentrations at the tips of the shear bands. In side-view observations, evidence was found of slip bands typically associated with dislocation channeling. No differences due to pre-irradiation heat treatment and heat-to-heat composition variations were detected. The only deviation from this behavior was found in V-4Cr-4Ti-B alloy, which failed in the grip portion by complete cleavage cracking.

  2. Analysis of Fracturing Network Evolution Behaviors in Random Naturally Fractured Rock Blocks (United States)

    Wang, Y.; Li, X.; Zhang, B.


    Shale gas has been discovered in the Upper Triassic Yanchang Formation, Ordos Basin, China. Due to the weak tectonic activities in the shale plays, core observations indicate abundant random non-tectonic micro-fractures in the producing shales. The role of micro-fractures in hydraulic fracturing for shale gas development is currently poorly understood yet potentially critical. In a series of scaled true triaxial laboratory experiments, we investigate the interaction of propagating fracturing network with natural fractures. The influence of dominating factors was studied and analyzed, with an emphasis on non-tectonic fracture density, injection rate, and stress ratio. A new index of P-SRV is proposed to evaluate the fracturing effectiveness. From the test results, three types of fracturing network geometry of radial random net-fractures, partly vertical fracture with random branches, and vertical main fracture with multiple branches were observed. It is suggested from qualitative and quantitative analysis that great micro-fracture density and injection rate tend to maximum the fracturing network; however, it tends to decrease the fracturing network with the increase in horizontal stress ratio. The function fitting results further proved that the injection rate has the most obvious influence on fracturing effectiveness.

  3. Hoffa fracture associated with ipsilateral femoral shaft fracture: clinical feature and treatment. (United States)

    Gong, Yu-Bao; Li, Qing-Song; Yang, Chen; Li, Shu-Qiang; Liu, Jian-Guo; Qi, Xin


    Hoffa fracture associated with ipsilateral femoral shaft fracture is very rare. Three cases of this rare type of injury were retrospectively reviewed. The sites of femoral shaft fractures and Hoffa fractures were documented. All femoral shaft fractures were managed with internal fixation. The rate of misdiagnosis for the Hoffa fractures was documented. Functions of the affected knees were evaluated according to the modified Hospital for Special Surgery (HSS) scores at two years follow-up. Femoral fractures were either transverse or composite in all three cases. Ipsilateral Hoffa fractures occurred at medial condyle in two cases, and lateral condyle in one case. Only one Hoffa fracture was identified preoperatively. All the femoral shaft fractures healed uneventfully. In the patient whose Hoffa fracture was correctly diagnosed, the modified HSS score was 94. In another patient, whose Hoffa fracture was treated by a second operation, the modified HSS score was 93. And in the third case, who refused additional operation for the Hoffa fracture, the modified HSS score was only 70. Conclusively femoral shaft fracture can be associated with ipsilateral Hoffa fracture, especially in motorcycle accident. This type of injury is very rare and misdiagnosis is common.

  4. Hoffa fracture associated with ipsilateral femoral shaft fracture: clinical feature and treatment

    Institute of Scientific and Technical Information of China (English)

    GONG Yu-bao; LI Qing-song; YANG Chen; LI Shu-qiang; LIU Jian-guo; QI Xin


    Hoffa fracture associated with ipsilateral femoral shaft fracture is very rare.Three cases of this rare type of injury were retrospectively reviewed.The sites of femoral shaft fractures and Hoffa fractures were documented.All femoral shaft fractures were managed with internal fixation.The rate of misdiagnosis for the Hoffa fractures was documented.Functions of the affected knees were evaluated according to the modified Hospital for Special Surgery (HSS) scores at two years follow-up.Femoral fractures were either transverse or composite in all three cases.Ipsilateral Hoffa fractures occurred at medial condyle in two cases,and lateral condyle in one case.Only one Hoffa fracture was identified preoperatively.All the femoral shaft fractures healed uneventfully.In the patient whose Hoffa fracture was correctly diagnosed,the modified HSS score was 94.In another patient,whose Hoffa fracture was treated by a second operation,the modified HSS score was 93.And in the third case,who refused additional operation for the Hoffa fracture,the modified HSS score was only 70.Conclusively femoral shaft fracture can be associated with ipsilateral Hoffa fracture,especially in motorcycle accident.This type of injury is very rare and misdiagnosis is common.

  5. Evaluation of fracture models through pressurized-thermal-shock testing

    Energy Technology Data Exchange (ETDEWEB)

    Pugh, C.E.; Bryan, R.H.; Bass, B.R.; Nanstad, R.K.


    Two multiple-transient pressurized-thermal-shock experiments (PTSEs) have been conducted under the NRC-sponsored Heavy-Section Steel Technology (HSST) program. The first test (PTSE-1) employed an SA-508 class 2 steel with high Charpy upper-shelf energy level and a relatively high brittle-to-ductile transition temperature. The second test (PTSE-2) used a 2 1/4 Cr-1 Mo steel (SA-387 grade 22) that had been given a special heat treatment to yield a low Charpy upper-shelf energy level and attendant low tearing resistance. Each experiment included two combined thermal and pressure transients that give rise to propagation and arrest of an initial long flaw that extended about 10% through the thick wall of the test cylinder. Both materials exhibited the ability to inhibit crack propagation by warm prestressing, high initiation toughness values and high crack-arrest toughness values. Cleavage initiation and arrest are modeled well by available fracture theories. However, calculations of ductile tearing based on resistance curves did not consistently predict the observed tearing.

  6. A 20 Residues Motif Delineates the Furin Cleavage Site and its Physical Properties May Influence Viral Fusion

    Directory of Open Access Journals (Sweden)

    Sun Tian


    Full Text Available Furin is a proprotein convertase that proteolytically cleaves protein precursors to yield functional proteins. Efficient cleavage depends on the presence of a specific sequence motif on the substrate. Currently, the cleavage site motif is described as a four amino acid pattern: R-X-[K/R]-R↓. However, not all furin cleavage recognition sites can be described by this pattern and not all R-X-[K/R]-R↓ sites are cleaved by furin. Since many furin substrates are involved in the pathogenesis of viral infection and human diseases, it is important to accurately characterize the furin cleavage site motif. In this study, the furin cleavage site motif was characterized using statistical analysis. The data were interpreted within the 3D crystal structure of the furin catalytic domain. The results indicate that the furin cleavage site motif is comprised of about 20 residues, P14–P6´. Specific physical properties such as volume, charge, and hydrophilicity are required at specific positions. The furin cleavage site motif is divided into two parts: 1 one core region (8 amino acids, positions P6–P2´ packed inside the furin binding pocket; 2 two polar regions (8 amino acids, positions P7–P14; and 4 amino acids, positions P3´–P6´ located outside the furin binding pocket. The physical properties of the core region contribute to the binding strength of the furin substrate, while the polar regions provide a solvent accessible environment and facilitate the accessibility of the core region to the furin binding pocket. This furin cleavage site motif also revealed a dynamic relationship linking the evolution of physical properties in region P1´–P6´ of viral fusion peptides, furin cleavage efficacy, and viral infectivity.

  7. Entropic origin of cobalt-carbon bond cleavage catalysis in adenosylcobalamin-dependent ethanolamine ammonia-lyase. (United States)

    Wang, Miao; Warncke, Kurt


    Adenosylcobalamin-dependent enzymes accelerate the cleavage of the cobalt-carbon (Co-C) bond of the bound coenzyme by >10(10)-fold. The cleavage-generated 5'-deoxyadenosyl radical initiates the catalytic cycle by abstracting a hydrogen atom from substrate. Kinetic coupling of the Co-C bond cleavage and hydrogen-atom-transfer steps at ambient temperatures has interfered with past experimental attempts to directly address the factors that govern Co-C bond cleavage catalysis. Here, we use time-resolved, full-spectrum electron paramagnetic resonance spectroscopy, with temperature-step reaction initiation, starting from the enzyme-coenzyme-substrate ternary complex and (2)H-labeled substrate, to study radical pair generation in ethanolamine ammonia-lyase from Salmonella typhimurium at 234-248 K in a dimethylsulfoxide/water cryosolvent system. The monoexponential kinetics of formation of the (2)H- and (1)H-substituted substrate radicals are the same, indicating that Co-C bond cleavage rate-limits radical pair formation. Analysis of the kinetics by using a linear, three-state model allows extraction of the microscopic rate constant for Co-C bond cleavage. Eyring analysis reveals that the activation enthalpy for Co-C bond cleavage is 32 ± 1 kcal/mol, which is the same as for the cleavage reaction in solution. The origin of Co-C bond cleavage catalysis in the enzyme is, therefore, the large, favorable activation entropy of 61 ± 6 cal/(mol·K) (relative to 7 ± 1 cal/(mol·K) in solution). This represents a paradigm shift from traditional, enthalpy-based mechanisms that have been proposed for Co-C bond-breaking in B12 enzymes. The catalysis is proposed to arise from an increase in protein configurational entropy along the reaction coordinate.

  8. Bisphosphonate-associated atypical subtrochanteric femur fracture. (United States)

    Wolin, Ely A; Banks, Kevin P; Vroman, Penny J


    Bisphosphonates help prevent progressive bone mineralization loss and subsequent osteoporotic fractures. However, long-term bisphosphonate therapy paradoxically increases the risk of a unique injury called an atypical subtrochanteric femur fracture. Despite this, the benefits of bisphosphonates outweigh the risks, because far more pathologic fractures are prevented than induced. The early identification of atypical subtrochanteric femur fractures is important as there is high associated morbidity and mortality. We describe a case of a 76-y-old woman with a completed bisphosphonate-associated atypical subtrochanteric femur fracture.

  9. Pulsative hematoma: A penile fracture complication

    Directory of Open Access Journals (Sweden)

    Nale Đorđe


    Full Text Available Background. Fracture of the penis is a direct blunt trauma of the erect or semi-erect penis. It can be treated by conservative or surgical means. Retrospective analyses of conservative penile fracture treatment reveal frequent immediate and later complications. Case report. We presented a 41- year-old patient with pulsative hematoma caused by an unusual fracture of the penis. Fracture had appeared 40 days before the admittance during a sexual intercourse. The patient was treated surgically. Conclusion. Pulsative hematoma (pulsative diverticulum is a very rare, early complication of a conservatively treated penile fracture. Surgical treatment has an advantage over surgical one, which was confirmed by our case report.


    Energy Technology Data Exchange (ETDEWEB)

    Lam, P; Prof. Yuh J. Chao, P


    The meaning of the phrase 'constraint effect in fracture' has changed in the past two decades from 'contained plasticity' to a broader description of 'dependence of fracture toughness value on geometry of test specimen or structure'. This paper will first elucidate the fundamental mechanics reasons for the apparent 'constraint effects in fracture', followed by outlining a straightforward approach to overcoming this problem in both brittle (elastic) and ductile (elastic-plastic) fracture. It is concluded by discussing the major difference in constraint effect on fracture event in elastic and elastic-plastic materials.

  11. Geomechanical Simulation of Fluid-Driven Fractures

    Energy Technology Data Exchange (ETDEWEB)

    Makhnenko, R.; Nikolskiy, D.; Mogilevskaya, S.; Labuz, J.


    The project supported graduate students working on experimental and numerical modeling of rock fracture, with the following objectives: (a) perform laboratory testing of fluid-saturated rock; (b) develop predictive models for simulation of fracture; and (c) establish educational frameworks for geologic sequestration issues related to rock fracture. These objectives were achieved through (i) using a novel apparatus to produce faulting in a fluid-saturated rock; (ii) modeling fracture with a boundary element method; and (iii) developing curricula for training geoengineers in experimental mechanics, numerical modeling of fracture, and poroelasticity.

  12. Differential cleavage of IRES trans-acting factors (ITAFs) in cells infected by human rhinovirus. (United States)

    Chase, Amanda J; Semler, Bert L


    Human rhinovirus (HRV) is a major causative agent of the common cold, and thus has several important health implications. As a member of the picornavirus family, HRV has a small genomic RNA that utilizes several host cell proteins for RNA replication. Host proteins poly(rC) binding protein 2 (PCBP2) and polypyrimidine tract binding protein (PTB) are cleaved by a viral proteinase during the course of infection by the related picornavirus, poliovirus. The cleavage of PCBP2 and PTB inhibits poliovirus translation and has been proposed to mediate a switch in poliovirus template usage from translation to RNA replication. HRV RNA replication also requires a switch in template usage from translation to RNA replication; however, the mechanism is not yet known. We demonstrate that PCBP2 and PTB are differentially cleaved during HRV infection in different cell lines, suggesting that HRV utilizes a mechanism distinct from PCBP2 or PTB cleavage to mediate a switch in template usage.

  13. Apoptosis Mediated by HIV Protease is Preceded by Cleavage of Bcl-2 (United States)

    Strack, Peter R.; West Frey, Michelle; Rizzo, Christopher J.; Cordova, Beverly; George, Henry J.; Meade, Raymond; Ho, Siew Peng; Corman, Jeanne; Tritch, Radonna; Korant, Bruce D.


    Expression of the human immunodeficiency virus type 1 (HIV) protease in cultured cells leads to apoptosis, preceded by cleavage of bcl-2, a key negative regulator of cell death. In contrast, a high level of bcl-2 protects cells in vitro and in vivo from the viral protease and prevents cell death following HIV infection of human lymphocytes, while reducing the yields of viral structural proteins, infectivity, and tumor necrosis factor α . We present a model for HIV replication in which the viral protease depletes the infected cells of bcl-2, leading to oxidative stress-dependent activation of NFkappa B, a cellular factor required for HIV transcription, and ultimately to cell death. Purified bcl-2 is cleaved by HIV protease between phenylalanine 112 and alanine 113. The results suggest a new option for HIV gene therapy; bcl-2 muteins that have noncleavable alterations surrounding the HIV protease cleavage site.

  14. Structural basis for duplex RNA recognition and cleavage by Archaeoglobus fulgidus C3PO (United States)

    Parizotto, Eneida A; Lowe, Edward D; Parker, James S


    Oligomeric complexes of Trax and Translin proteins, known as C3POs, participate in a variety of eukaryotic nucleic acid metabolism pathways including RNAi and tRNA processing. In RNAi in humans and Drosophila, C3PO activates pre-RISC by removing the passenger strand of the siRNA precursor duplex using nuclease activity present in Trax. It is not known how C3POs engage with nucleic acid substrates. Here we identify a single protein from Archaeoglobus fulgidus that assembles into an octamer with striking similarity to human C3PO. The structure in complex with duplex RNA reveals that the octamer entirely encapsulates a single thirteen base-pair RNA duplex inside a large inner cavity. Trax-like subunit catalytic sites target opposite strands of the duplex for cleavage, separated by seven base pairs. The structure provides insight into the mechanism of RNA recognition and cleavage by an archaeal C3PO-like complex. PMID:23353787

  15. Structures of a CRISPR-Cas9 R-loop complex primed for DNA cleavage. (United States)

    Jiang, Fuguo; Taylor, David W; Chen, Janice S; Kornfeld, Jack E; Zhou, Kaihong; Thompson, Aubri J; Nogales, Eva; Doudna, Jennifer A


    Bacterial adaptive immunity and genome engineering involving the CRISPR (clustered regularly interspaced short palindromic repeats)-associated (Cas) protein Cas9 begin with RNA-guided DNA unwinding to form an RNA-DNA hybrid and a displaced DNA strand inside the protein. The role of this R-loop structure in positioning each DNA strand for cleavage by the two Cas9 nuclease domains is unknown. We determine molecular structures of the catalytically active Streptococcus pyogenes Cas9 R-loop that show the displaced DNA strand located near the RuvC nuclease domain active site. These protein-DNA interactions, in turn, position the HNH nuclease domain adjacent to the target DNA strand cleavage site in a conformation essential for concerted DNA cutting. Cas9 bends the DNA helix by 30°, providing the structural distortion needed for R-loop formation.

  16. Synthesis, photochemistry, DNA cleavage/binding and cytotoxic properties of fluorescent quinoxaline and quinoline hydroperoxides. (United States)

    Chowdhury, Nilanjana; Gangopadhyay, Moumita; Karthik, S; Pradeep Singh, N D; Baidya, Mithu; Ghosh, S K


    Novel fluorescent quinoxaline and quinoline hydroperoxides were shown to perform dual role as both fluorophores for cell imaging and photoinduced DNA cleaving agents. Photophysical studies of newly synthesized quinoxaline and quinoline hydroperoxides showed that they all exhibited moderate to good fluorescence. Photolysis of quinoxaline and quinoline hydroperoxides in acetonitrile using UV light above 350nm resulted in the formation of corresponding ester compounds via γ-hydrogen abstraction by excited carbonyl chromophore. Single strand DNA cleavage was achieved on irradiation of newly synthesized hydroperoxides by UV light (⩾350nm). Both hydroxyl radicals and singlet oxygen were identified as reactive oxygen species (ROS) responsible for the DNA cleavage. Further, we showed quinoline hydroperoxide binds to ct-DNA via intercalative mode. In vitro biological studies revealed that quinoline hydroperoxide has good biocompatibility, cellular uptake property and cell imaging ability. Finally, we showed that quinoline hydroperoxide can permeate into cells efficiently and may cause cytotoxicity upon irradiation by UV light.

  17. Mercury Detoxification by Bacteria: Simulations of Transcription Activation and Mercury-Carbon Bond Cleavage

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Hao-Bo [ORNL; Parks, Jerry M [ORNL; Johs, Alexander [ORNL; Smith, Jeremy C [ORNL


    In this chapter, we summarize recent work from our laboratory and provide new perspective on two important aspects of bacterial mercury resistance: the molecular mechanism of transcriptional regulation by MerR, and the enzymatic cleavage of the Hg-C bond in methylmercury by the organomercurial lyase, MerB. Molecular dynamics (MD) simulations of MerR reveal an opening-and-closing dynamics, which may be involved in initiating transcription of mercury resistance genes upon Hg(II) binding. Density functional theory (DFT) calculations on an active-site model of the enzyme reveal how MerB catalyzes the Hg-C bond cleavage using cysteine coordination and acid-base chemistry. These studies provide insight into the detailed mechanisms of microbial gene regulation and defense against mercury toxicity.

  18. VAMP/synaptobrevin cleavage by tetanus and botulinum neurotoxins is strongly enhanced by acidic liposomes. (United States)

    Caccin, Paola; Rossetto, Ornella; Rigoni, Michela; Johnson, Eric; Schiavo, Giampietro; Montecucco, Cesare


    Tetanus and botulinum neurotoxins (TeNT and BoNTs) block neuroexocytosis via specific cleavage and inactivation of SNARE proteins. Such activity is exerted by the N-terminal 50 kDa light chain (L) domain, which is a zinc-dependent endopeptidase. TeNT, BoNT/B, /D, /F and /G cleave vesicle associated membrane protein (VAMP), a protein of the neurotransmitter-containing small synaptic vesicles, at different single peptide bonds. Since the proteolytic activity of these metalloproteases is higher on native VAMP inserted in synaptic vesicles than on recombinant VAMP, we have investigated the influence of liposomes of different lipid composition on this activity. We found that the rate of VAMP cleavage with all neurotoxins tested here is strongly enhanced by negatively charged lipid mixtures. This effect is at least partially due to the binding of the metalloprotease to the lipid membranes, with electrostatic interactions playing an important role.

  19. Polarity and cell division orientation in the cleavage embryo: from worm to human (United States)

    Ajduk, Anna; Zernicka-Goetz, Magdalena


    Cleavage is a period after fertilization, when a 1-cell embryo starts developing into a multicellular organism. Due to a series of mitotic divisions, the large volume of a fertilized egg is divided into numerous smaller, nucleated cells—blastomeres. Embryos of different phyla divide according to different patterns, but molecular mechanism of these early divisions remains surprisingly conserved. In the present paper, we describe how polarity cues, cytoskeleton and cell-to-cell communication interact with each other to regulate orientation of the early embryonic division planes in model animals such as Caenorhabditis elegans, Drosophila and mouse. We focus particularly on the Par pathway and the actin-driven cytoplasmic flows that accompany it. We also describe a unique interplay between Par proteins and the Hippo pathway in cleavage mammalian embryos. Moreover, we discuss the potential meaning of polarity, cytoplasmic dynamics and cell-to-cell communication as quality biomarkers of human embryos. PMID:26660321

  20. Histidine-Based Lipopeptides Enhance Cleavage of Nucleic Acids: Interactions with DNA and Hydrolytic Properties. (United States)

    Bélières, M; Déjugnat, C; Chouini-Lalanne, N


    Interaction studies and cleavage activity experiments were carried out between plasmid DNA and a series of histidine-based lipopeptides. Specific fluorescent probes (ethidium bromide, Hoechst 33342, and pyrene) were used to monitor intercalation, minor groove binding, and self-assembly of lipopeptides, respectively. Association between DNA and lipopeptides was thus evidenced, highlighting the importance of both histidine and hydrophobic tail in the interaction process. DNA cleavage in the presence of lipopeptides was then detected by gel electrophoresis and quantified, showing the importance of histidine and the involvement of its side-chain imidazole in the hydrolysis mechanism. These systems could then be developed as synthetic nucleases while raising concern of introducing histidine in the design of lipopeptide-based transfection vectors.

  1. Exchanging Alkyl Groups through Unstrained C-C Bond Cleavage in the Presence of a Copper Catalyst. (United States)

    Wada, Masaru; Noda, Yushi; Nishikata, Takashi


    Although numerous reports exist on strained C-C bond cleavage reactions in aryl substitutions, the cleavage methodology for unstrained C-C bonds in alkylation reactions has not yet been established. We found that unstrained allylic C-C bonds can be cleaved using α-radicals to form C(sp(3) )-C(sp(3) ) bonds in the presence of a copper catalyst. In this reaction, the property of leaving and loading radicals is very important for radical fragmentations. In this paper, we investigated the effects of these properties in cleavage reactions for unstrained C-C bonds.

  2. cis-Apa: a practical linker for the microwave-assisted preparation of cyclic pseudopeptides via RCM cyclative cleavage. (United States)

    Baron, Alice; Verdié, Pascal; Martinez, Jean; Lamaty, Frédéric


    A new linker cis-5-aminopent-3-enoic acid (cis-Apa) was prepared for the synthesis of cyclic pseudopeptides by cyclization-cleavage by using ring-closing methatesis (RCM). We developed a new synthetic pathway for the preparation of the cis-Apa linker that was tested in the cyclization-cleavage process of different RGD peptide sequences. Different macrocyclic peptidomimetics were prepared by using this integrated microwave-assisted method, showing that the readily available cis-Apa amino acid is well adapted as a linker in the cyclization-cleavage process.

  3. ChloroP, a neural network-based method for predicting chloroplast transitpeptides and their cleavage sites

    DEFF Research Database (Denmark)

    Emanuelsson, O.; Nielsen, Henrik; von Heijne, Gunnar


    We present a neural network based method (ChloroP) for identifying chloroplast transit peptides and their cleavage sites. Using cross-validation, 88% of the sequences in our homology reduced training set were correctly classified as transit peptides or nontransit peptides. This performance level...... is well above that of the publicly available chloroplast localization predictor PSORT. Cleavage sites are predicted using a scoring matrix derived by an automatic motif-finding algorithm. Approximately 60% of the known cleavage sites in our sequence collection were predicted to within +/-2 residues from...

  4. Secologanin synthase which catalyzes the oxidative cleavage of loganin into secologanin is a cytochrome P450. (United States)

    Yamamoto, H; Katano, N; Ooi, A; Inoue, K


    Secologanin synthase, an enzyme catalyzing the oxidative cleavage of the cyclopentane ring in loganin to form secologanin, was detected in microsomal preparations from cell suspension cultures of Lonicera japonica. The reaction required NADPH and molecular oxygen, and was blocked by carbon monoxide as well as by several other cytochrome P450 inhibitors, indicating that the reaction was mediated by cytochrome P450. Of the substrates examined, only specificity for loganin was demonstrated. A possible reaction mechanism is described.

  5. Unexpected cleavage of 2-azido-2-(hydroxymethyl)oxetanes: conformation determines reaction pathway? (United States)

    Farber, Elisa; Herget, Jackson; Gascón, José A; Howell, Amy R


    An unanticipated cleavage of 2-azido-2-(hydroxymethyl)oxetanes is reported. In attempts to oxidize the title oxetanyl alcohols to the corresponding carboxylic acids with RuO4, cleaved nitriles were formed as the sole isolable products, while a closely related tetrahydrofuran gave solely the expected carboxylic acid. Quantum chemical calculations suggest that the divergent outcomes are governed by conformational differences in the azidoalcohols.

  6. Carbon–carbon bond cleavage for Cu-mediated aromatic trifluoromethylations and pentafluoroethylations

    Directory of Open Access Journals (Sweden)

    Tsuyuka Sugiishi


    Full Text Available This short review highlights the copper-mediated fluoroalkylation using perfluoroalkylated carboxylic acid derivatives. Carbon–carbon bond cleavage of perfluoroalkylated carboxylic acid derivatives takes place in fluoroalkylation reactions at high temperature (150–200 °C or under basic conditions to generate fluoroalkyl anion sources for the formation of fluoroalkylcopper species. The fluoroalkylation reactions, which proceed through decarboxylation or tetrahedral intermediates, are useful protocols for the synthesis of fluoroalkylated aromatics.

  7. A strategy for developing a hammerhead ribozyme for selective RNA cleavage depending on substitutional RNA editing. (United States)

    Fukuda, Masatora; Kurihara, Kei; Tanaka, Yasuyoshi; Deshimaru, Masanobu


    Substitutional RNA editing plays a crucial role in the regulation of biological processes. Cleavage of target RNA that depends on the specific site of substitutional RNA editing is a useful tool for analyzing and regulating intracellular processes related to RNA editing. Hammerhead ribozymes have been utilized as small catalytic RNAs for cleaving target RNA at a specific site and may be used for RNA-editing-specific RNA cleavage. Here we reveal a design strategy for a hammerhead ribozyme that specifically recognizes adenosine to inosine (A-to-I) and cytosine to uracil (C-to-U) substitutional RNA-editing sites and cleaves target RNA. Because the hammerhead ribozyme cleaves one base upstream of the target-editing site, the base that pairs with the target-editing site was utilized for recognition. RNA-editing-specific ribozymes were designed such that the recognition base paired only with the edited base. These ribozymes showed A-to-I and C-to-U editing-specific cleavage activity against synthetic serotonin receptor 2C and apolipoprotein B mRNA fragments in vitro, respectively. Additionally, the ribozyme designed for recognizing A-to-I RNA editing at the Q/R site on filamin A (FLNA) showed editing-specific cleavage activity against physiologically edited FLNA mRNA extracted from cells. We demonstrated that our strategy is effective for cleaving target RNA in an editing-dependent manner. The data in this study provided an experimental basis for the RNA-editing-dependent degradation of specific target RNA in vivo.

  8. Manipulations of Amyloid Precursor Protein Cleavage Disrupt the Circadian Clock in Aging Drosophila


    Blake, Matthew R.; Holbrook, Scott D.; Kotwica-Rolinska, Joanna; Chow, Eileen; Kretzschmar, Doris; Giebultowicz, Jadwiga M.


    Alzheimer’s disease (AD) is a neurodegenerative disease characterized by severe cognitive deterioration. While causes of AD pathology are debated, a large body of evidence suggests that increased cleavage of Amyloid Precursor Protein (APP) producing the neurotoxic Amyloid-β (Aβ) peptide plays a fundamental role in AD pathogenesis. One of the detrimental behavioral symptoms commonly associated with AD is the fragmentation of sleep-activity cycles with increased nighttime activity and daytime n...

  9. Aerobic dehydrogenative α-diarylation of benzyl ketones with aromatics through carbon-carbon bond cleavage. (United States)

    More, Nagnath Yadav; Jeganmohan, Masilamani


    Substituted benzyl ketones reacted with aromatics in the presence of K2S2O8 in CF3COOH at room temperature, yielding α-diaryl benzyl ketones through a carbon-carbon bond cleavage. In the reaction, two new carbon-carbon bonds were formed and one carbon-carbon bond was cleaved. It is very interesting that two different nucleophiles such as benzyl ketones and aromatics were coupled together without metal, which is unusual in organic synthesis.

  10. Signal peptide discrimination and cleavage site identification using SVM and NN. (United States)

    Kazemian, H B; Yusuf, S A; White, K


    About 15% of all proteins in a genome contain a signal peptide (SP) sequence, at the N-terminus, that targets the protein to intracellular secretory pathways. Once the protein is targeted correctly in the cell, the SP is cleaved, releasing the mature protein. Accurate prediction of the presence of these short amino-acid SP chains is crucial for modelling the topology of membrane proteins, since SP sequences can be confused with transmembrane domains due to similar composition of hydrophobic amino acids. This paper presents a cascaded Support Vector Machine (SVM)-Neural Network (NN) classification methodology for SP discrimination and cleavage site identification. The proposed method utilises a dual phase classification approach using SVM as a primary classifier to discriminate SP sequences from Non-SP. The methodology further employs NNs to predict the most suitable cleavage site candidates. In phase one, a SVM classification utilises hydrophobic propensities as a primary feature vector extraction using symmetric sliding window amino-acid sequence analysis for discrimination of SP and Non-SP. In phase two, a NN classification uses asymmetric sliding window sequence analysis for prediction of cleavage site identification. The proposed SVM-NN method was tested using Uni-Prot non-redundant datasets of eukaryotic and prokaryotic proteins with SP and Non-SP N-termini. Computer simulation results demonstrate an overall accuracy of 0.90 for SP and Non-SP discrimination based on Matthews Correlation Coefficient (MCC) tests using SVM. For SP cleavage site prediction, the overall accuracy is 91.5% based on cross-validation tests using the novel SVM-NN model.

  11. Proteolytic cleavage of cadherins: Functional role of the cleaved extracellular and cytoplasmic domains



    Dynamic regulation of cadherin mediated cell-cell adhesion is crucial for morphogenesis and tissue homeostasis. Cadherin adhesive function can be regulated by distinct proteolytic cleavage events, resulting in release of either the ectodomain or cytoplasmic domain. However, it is unclear if the released fragments have biological activity by themselves. This thesis analyses the functional significance of the generated cadherin fragments. Using Xenopus laevis development as model system, it was...

  12. Cleavage of serum response factor mediated by enteroviral protease 2A contributes to impaired cardiac function

    Institute of Scientific and Technical Information of China (English)

    Jerry Wong; Jingchun Zhang; Bobby Yanagawa; Zongshu Luo; Xiangsheng Yang; Jiang Chang; Bruce McManus; Honglin Luo


    Enteroviral infection can lead to dilated cardiomyopathy (DCM),which is a major cause of cardiovascular mortality worldwide.However,the pathogenetic mechanisms have not been fully elucidated.Serum response factor (SRF) is a cardiac-enriched transcription regulator controlling the expression of a variety of target genes,including those involved in the contractile apparatus and immediate early response,as well as microRNAs that silence the expression of cardiac regulatory factors.Knockout of SRF in the heart results in downregulation of cardiac contractile gene expression and development of DCM.The goal of this study is to understand the role of SRF in enterovirus-induced cardiac dysfunction and progression to DCM.Here we report that SRF is cleaved following enteroviral infection of mouse heart and cultured cardiomyocytes.This cleavage is accompanied by impaired cardiac function and downregulation of cardiac-specific contractile and regulatory genes.Further investigation by antibody epitope mapping and site-directed mutagenesis demonstrates that SRF cleavage occurs at the region of its transactivation domain through the action of virus-encoded protease 2A.Moreover,we demonstrate that cleavage of SRF dissociates its transactivation domain from DNA-binding domain,resulting in the disruption of SRF-mediated gene transactivation.In addition to loss of functional SRF,finally we report that the N-terminal fragment of SRF cleavage products can also act as a dominant-negative transcription factor,which likely competes with the native SRF for DNA binding.Our results suggest a mechanism by which virus infection impairs heart function and may offer a new therapeutic strategy to ameliorate myocardial damage and progression to DCM.

  13. Mechanistic Insights into Ring Cleavage and Contraction of Benzene over a Titanium Hydride Cluster. (United States)

    Kang, Xiaohui; Luo, Gen; Luo, Lun; Hu, Shaowei; Luo, Yi; Hou, Zhaomin


    Carbon-carbon bond cleavage of benzene by transition metals is of great fundamental interest and practical importance, as this transformation is involved in the production of fuels and other important chemicals in the industrial hydrocracking of naphtha on solid catalysts. Although this transformation is thought to rely on cooperation of multiple metal sites, molecular-level information on the reaction mechanism has remained scarce to date. Here, we report the DFT studies of the ring cleavage and contraction of benzene by a molecular trinuclear titanium hydride cluster. Our studies suggest that the reaction is initiated by benzene coordination, followed by H2 release, C6H6 hydrometalation, repeated C-C and C-H bond cleavage and formation to give a MeC5H4 unit, and insertion of a Ti atom into the MeC5H4 unit with release of H2 to give a metallacycle product. The C-C bond cleavage and ring contraction of toluene can also occur in a similar fashion, though some details are different due to the presence of the methyl substituent. Obviously, the facile release of H2 from the metal hydride cluster to provide electrons and to alter the charge population at the metal centers, in combination with the flexible metal-hydride connections and dynamic redox behavior of the trimetallic framework, has enabled this unusual transformation to occur. This work has not only provided unprecedented insights into the activation and transformation of benzene over a multimetallic framework but it may also offer help in the design of new molecular catalysts for the activation and transformation of inactive aromatics.

  14. Inhibition of influenza virus infection and hemagglutinin cleavage by the protease inhibitor HAI-2

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, Brian S.; Chung, Changik; Cyphers, Soreen Y.; Rinaldi, Vera D.; Marcano, Valerie C.; Whittaker, Gary R., E-mail:


    Highlights: • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza HA cleavage activation. • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza virus infection. • Comparative analysis of HAI-2 for vesicular stomatitis virus and human parainfluenza virus type-1. • Analysis of the activity of HAI-2 in a mouse model of influenza. - Abstract: Influenza virus remains a significant concern to public health, with the continued potential for a high fatality pandemic. Vaccination and antiviral therapeutics are effective measures to circumvent influenza virus infection, however, multiple strains have emerged that are resistant to the antiviral therapeutics currently on the market. With this considered, investigation of alternative antiviral therapeutics is being conducted. One such approach is to inhibit cleavage activation of the influenza virus hemagglutinin (HA), which is an essential step in the viral replication cycle that permits viral-endosome fusion. Therefore, targeting trypsin-like, host proteases responsible for HA cleavage in vivo may prove to be an effective therapeutic. Hepatocyte growth factor activator inhibitor 2 (HAI-2) is naturally expressed in the respiratory tract and is a potent inhibitor of trypsin-like serine proteases, some of which have been determined to cleave HA. In this study, we demonstrate that HAI-2 is an effective inhibitor of cleavage of HA from the human-adapted H1 and H3 subtypes. HAI-2 inhibited influenza virus H1N1 infection in cell culture, and HAI-2 administration showed protection in a mouse model of influenza. HAI-2 has the potential to be an effective, alternative antiviral therapeutic for influenza.

  15. Effects of fracture reactivation and diagenesis on fracture network evolution: Cambrian Eriboll Formation, NW Scotland (United States)

    Hooker, J. N.; Eichhubl, P.; Xu, G.; Ahn, H.; Fall, A.; Hargrove, P.; Laubach, S.; Ukar, E.


    The Cambrian Eriboll Formation quartzarenites contain abundant fractures with varying degrees of quartz cement infill. Fractures exist that are entirely sealed; are locally sealed by bridging cements but preserve pore space among bridges; are mostly open but lined with veneers of cement; or are devoid of cement. Fracture propagation in the Eriboll Formation is highly sensitive to the presence of pre-existing fractures. Fracture reactivation occurs in opening mode as individual fractures repeatedly open and are filled or bridged by syn-kinematic cements. As well, reactivation occurs in shear as opening of one fracture orientation coincides with shear displacement along pre-existing fractures of different orientations. The tendency for pre-existing fractures to slip varies in part by the extent of cement infill, yet we observe shear and opening-mode reactivation even among sealed fractures. Paleotemperature analysis of fluid inclusions within fracture cements suggests some fractures now in outcrop formed deep in the subsurface. Fractures within the Eriboll Formation may therefore affect later fracture propagation throughout geologic time. With progressive strain, fault zones develop within fracture networks by a sequence of opening-mode fracture formation, fracture reactivation and linkage, fragmentation, cataclasis, and the formation of slip surfaces. Cataclasite within fault zones is commonly more thoroughly cemented than fractures in the damage zone or outside the fault zone. This variance of cement abundance is likely the result of (1) continued exposure of freshly broken quartz surfaces within cataclasite, promoting quartz precipitation, and (2) possibly more interconnected pathways for mass transfer within the fault zone. Enhanced cementation of cataclasite results in strengthening or diagenetic strain hardening of the evolving fault zone. Further slip is accommodated by shear localization along discrete slip surfaces. With further linkage of fault segments

  16. Temporal bone fracture and its complications

    Institute of Scientific and Technical Information of China (English)


    Objective: To explore the characteristics and treatment oftemporal bone fractures and injuries in the medial-inner ear.Methods: The clinical data of 48 cases of temporal bone fractures admitted to our hospital from January 1989 to November 1999 were retrospectively analyzed.Results: Forty-eight patients with temporal bone fractures accounted for 17.00% of the homochronous craniofacial fractures. Of the 48 cases, temporal bone fractures induced by traffic accidents accounted for 66.67%, capillary fractures for 93.75%, medial-inner ear injuries or craniocerebral injuries for 77.08% and hearing loss or tinnitus for 48.00%. The cerebrospinal fluid (CSF) otorrhea and facioplegia accounted for 36.70% and 3.00%, respectively, in the longitudinal fractures, while they were 25.00% and 37.50%, respectively, in the transversal fractures. Primary emergent operations were performed on 46 cases and neurosurgery accounted for 46.00%. Secondary procedures accounted for 16.70%. As a result, 43 cases survived (89.58%) and 5 died (10.41%).Conclusions: Traffic injury is the first high-dangerous factor for temporal bone fractures, which are often complicated with medial-inner ear or craniocerebral injury. The CSF otorrhea is common in the longitudinal fractures and facioplegia is common in the transversal fractures. The key step is to rescue the life, keep the airway unobstructed and maintain the circulation in the primary emergency treatment.


    Energy Technology Data Exchange (ETDEWEB)

    Abbas Firoozabadi


    Numerical simulation of water injection in discrete fractured media with capillary pressure is a challenge. Dual-porosity models in view of their strength and simplicity can be mainly used for sugar-cube representation of fractured media. In such a representation, the transfer function between the fracture and the matrix block can be readily calculated for water-wet media. For a mixed-wet system, the evaluation of the transfer function becomes complicated due to the effect of gravity. In this work, they use a discrete-fracture model in which the fractures are discretized as one dimensional entities to account for fracture thickness by an integral form of the flow equations. This simple step greatly improves the numerical solution. Then the discrete-fracture model is implemented using a Galerkin finite element method. The robustness and the accuracy of the approach are shown through several examples. First they consider a single fracture in a rock matrix and compare the results of the discrete-fracture model with a single-porosity model. Then, they use the discrete-fracture model in more complex configurations. Numerical simulations are carried out in water-wet media as well as in mixed-wet media to study the effect of matrix and fracture capillary pressures.

  18. Modeling fracture porosity evolution in dolostone (United States)

    Gale, Julia F. W.; Lander, Robert H.; Reed, Robert M.; Laubach, Stephen E.


    Opening-mode fractures in dolostones buried to depths of ˜1-5 km contain synkinematic dolomite cement, the amount and internal structure of which has a systematic relationship to fracture size. Narrow fractures (cement or cement with a crack-seal texture that indicates multiple incremental openings. Wider fractures can preserve considerable effective porosity, but anomalously thick dolomite cement bridges are commonly present in fractures that are otherwise lined with a thin veneer of cement. Dolomite bridges resemble quartz bridges that are common in fractured sandstones. We developed a geometric crystal growth model for synkinematic dolomite fracture fill in fractured dolostones, where periodic incremental fracture-opening events are introduced with concurrent cement growth. We assumed constant temperature and supersaturation with respect to dolomite. A key assumption in the model is that rapid dolomite accumulation within bridges is governed by high cement-growth rates on repeatedly broken grain surfaces during the process of crack seal. Slower cement-growth rates occur on euhedral crystals. This assumption is made on the basis of a comparison with quartz cement growth in fractured sandstones. Simulations with different fracture-opening rates mimic bridge and lining cement morphologies, including characteristic rhombic shapes of dolomite bridges.

  19. Clavicle fractures - incidence of supraclavicular nerve injury

    Directory of Open Access Journals (Sweden)

    Pedro Jose Labronici


    Full Text Available OBJECTIVE: To analyze retrospectively 309 fractures in the clavicle and the relation with injury of the supraclavicular nerve after trauma. METHODS: It was analyzed 309 patients with 312 clavicle fractures. The Edinburgh classification was used. Four patients had fractures in the medial aspect of the clavicle, 33 in the lateral aspect and 272 in the diaphyseal aspect and three bilateral fractures. RESULTS: 255 patients were analyzed and five had paresthesia in the anterior aspect of the thorax. Four patients had type 2 B2 fracture and one type 2 B1 fracture. All patients showed spontaneous improvement, in the mean average of 3 months after the trauma. CONCLUSION: Clavicle fractures and/ or shoulder surgeries can injure the lateral, intermediary or medial branches of the supraclavicular nerve and cause alteration of sensibility in the anterior aspect of the thorax. Knowledge of the anatomy of the nerve branches helps avoid problems in this region.

  20. Osteoporotic fractures: a brain or bone disease? (United States)

    Birge, Stanley J


    Osteoporosis is a skeletal disorder that predisposes individuals to increased risk of fracture. However, most osteoporotic fractures occur in women who do not meet criteria for osteoporosis. Hence, bone density, by itself, is a relatively poor predictor of fracture. Age and age-related factors are now recognized as increasingly important in determining fracture risk. Osteoporotic fractures are associated with increased disability and mortality, suggesting that osteoporosis may be a clinical manifestation of an underlying disease process affecting multiple systems. The systems affected, the musculo-skeletal system and the central nervous system, are shared in many respects with the frailty syndrome. Vitamin D deficiency is a major contributor to the frailty syndrome, osteoporosis, and osteoporotic fractures. Its effects are mediated by the development of cerebrovascular disease, postural instability, muscle weakness, and bone fragility. Thus, osteoporotic fractures result from both a bone and brain disease.

  1. Cas9-catalyzed DNA Cleavage Generates Staggered Ends: Evidence from Molecular Dynamics Simulations (United States)

    Zuo, Zhicheng; Liu, Jin


    The CRISPR-associated endonuclease Cas9 from Streptococcus pyogenes (spCas9) along with a single guide RNA (sgRNA) has emerged as a versatile toolbox for genome editing. Despite recent advances in the mechanism studies on spCas9-sgRNA-mediated double-stranded DNA (dsDNA) recognition and cleavage, it is still unclear how the catalytic Mg2+ ions induce the conformation changes toward the catalytic active state. It also remains controversial whether Cas9 generates blunt-ended or staggered-ended breaks with overhangs in the DNA. To investigate these issues, here we performed the first all-atom molecular dynamics simulations of the spCas9-sgRNA-dsDNA system with and without Mg2+ bound. The simulation results showed that binding of two Mg2+ ions at the RuvC domain active site could lead to structurally and energetically favorable coordination ready for the non-target DNA strand cleavage. Importantly, we demonstrated with our simulations that Cas9-catalyzed DNA cleavage produces 1-bp staggered ends rather than generally assumed blunt ends.

  2. Reaction Pathways and Energetics of Etheric C–O Bond Cleavage Catalyzed by Lanthanide Triflates

    Energy Technology Data Exchange (ETDEWEB)

    Assary, Rajeev S.; Atesin, Abdurrahman C.; Li, Zhi; Curtiss, Larry A.; Marks, Tobin J.


    Efficient and selective cleavage of etheric C-O bonds is crucial for converting biomass into platform chemicals and liquid transportation fuels. In this contribution, computational methods at the DFT B3LYP level of theory are employed to understand the efficacy of lanthanide triflate catalysts (Ln(OTf)3, Ln = La, Ce, Sm, Gd, Yb, and Lu) in cleaving etheric C-O bonds. In agreement with experiment, the calculations indicate that the reaction pathway for C-O cleavage occurs via a C-H → O-H proton transfer in concert with weakening of the C-O bond of the coordinated ether substrate to ultimately yield a coordinated alkenol. The activation energy for this process falls as the lanthanide ionic radius decreases, reflecting enhanced metal ion electrophilicity. Details of the reaction mechanism for Yb(OTf)3-catalyzed ring opening are explored in depth, and for 1-methyl-d3-butyl phenyl ether, the computed primary kinetic isotope effect of 2.4 is in excellent agreement with experiment (2.7), confirming that etheric ring-opening pathway involves proton transfer from the methyl group alpha to the etheric oxygen atom, which is activated by the electrophilic lanthanide ion. Calculations of the catalytic pathway using eight different ether substrates indicate that the more rapid cleavage of acyclic versus cyclic ethers is largely due to entropic effects, with the former C-O bond scission processes increasing the degrees of freedom/particles as the transition state is approached.

  3. Reaction between radicals and N-alkoxyamines As coordinated cleavage with fragmentation (United States)

    Denisov, E. T.; Shestakov, A. F.


    Quantum chemical calculations of the enthalpy and activation energy of two reactions with MeO{2/⊙} attacking the CH- and CH2-groups of 2,2,6,6-tetramethylpiperidineoxy-2'-butane are performed. It is shown that the cleavage of hydrogen atoms is accompanied by coordinated breaking of N-O-bonds in the former case and C-O-bonds in the latter. Based on the obtained results, a new scheme is proposed for the cyclic mechanism behind the cleavage of chains on nitroxyl radicals in oxidizing hydrocarbons and polymers that agrees with experimental data. At the center of this cyclic mechanism lies the fast exothermic reaction between peroxyl radicals and N-alkoxyamine with the cleavage of H atoms and the coordinated fragmentation of molecules. Using the model of intersecting parabolas, an algorithm for calculating the enthalpies, activation energies, and rate constants of these reactions with the participation of alkyl, alkoxy, aminyl, peroxyl, phenoxyl, thiyl, and hydroxyl radicals is proposed.

  4. Analysis of the Proteolytic Processing of ABCA3: Identification of Cleavage Site and Involved Proteases.

    Directory of Open Access Journals (Sweden)

    Nicole Hofmann

    Full Text Available ABCA3 is a lipid transporter in the limiting membrane of lamellar bodies in alveolar type II cells. Mutations in the ABCA3 gene cause respiratory distress syndrome in new-borns and childhood interstitial lung disease. ABCA3 is N-terminally cleaved by an as yet unknown protease, a process believed to regulate ABCA3 activity.The exact site where ABCA3 is cleaved was localized using mass spectrometry (MS. Proteases involved in ABCA3 processing were identified using small molecule inhibitors and siRNA mediated gene knockdown. Results were verified by in vitro digestion of a synthetic peptide substrate mimicking ABCA3's cleavage region, followed by MS analysis.We found that cleavage of ABCA3 occurs after Lys174 which is located in the proteins' first luminal loop. Inhibition of cathepsin L and, to a lesser extent, cathepsin B resulted in attenuation of ABCA3 cleavage. Both enzymes showed activity against the ABCA3 peptide in vitro with cathepsin L being more active.We show here that, like some other proteins of the lysosomal membrane, ABCA3 is a substrate of cathepsin L. Therefore, cathepsin L may represent a potential target to therapeutically influence ABCA3 activity in ABCA3-associated lung disease.

  5. Porcine deltacoronavirus nsp5 inhibits interferon-β production through the cleavage of NEMO. (United States)

    Zhu, Xinyu; Fang, Liurong; Wang, Dang; Yang, Yuting; Chen, Jiyao; Ye, Xu; Foda, Mohamed Frahat; Xiao, Shaobo


    Porcine deltacoronavirus (PDCoV) causes acute enteric disease and mortality in seronegative neonatal piglets. Previously we have demonstrated that PDCoV infection suppresses the production of interferon-beta (IFN-β), while the detailed mechanisms are poorly understood. Here, we demonstrate that nonstructural protein 5 (nsp5) of PDCoV, the 3C-like protease, significantly inhibits Sendai virus (SEV)-induced IFN-β production by targeting the NF-κB essential modulator (NEMO), confirmed by the diminished function of NEMO cleaved by PDCoV. The PDCoV nsp5 cleavage site in the NEMO protein was identified as glutamine 231, and was identical to the porcine epidemic diarrhea virus nsp5 cleavage site, revealing the likelihood of a common target in NEMO for coronaviruses. Furthermore, this cleavage impaired the ability of NEMO to activate the IFN response and downstream signaling. Taken together, our findings reveal PDCoV nsp5 to be a newly identified IFN antagonist and enhance the understanding of immune evasion by deltacoronaviruses.

  6. Effects of 2'-O-methyl nucleotide substitution on EcoRI endonuclease cleavage activities.

    Directory of Open Access Journals (Sweden)

    Guojie Zhao

    Full Text Available To investigate the effect of sugar pucker conformation on DNA-protein interactions, we used 2'-O-methyl nucleotide (2'-OMeN to modify the EcoRI recognition sequence -TGAATTCT-, and monitored the enzymatic cleavage process using FRET method. The 2'-O-methyl nucleotide has a C3'-endo sugar pucker conformation different from the C2'-endo sugar pucker conformation of native DNA nucleotides. The initial reaction velocities were measured and the kinetic parameters, Km and Vmax were derived using Michaelis-Menten equation. Experimental results showed that 2'-OMeN substitutions for the EcoRI recognition sequence decreased the cleavage efficiency for A2, A3 and T4 substitutions significantly, and 2'-OMeN substitution for T5 residue inhibited the enzymatic activity completely. In contrast, substitutions for G1 and C6 could maintain the original activity. 2'-fluoro nucleic acid (2'-FNA and locked nucleic acid (LNA having similar C3'-endo sugar pucker conformation also demonstrated similar enzymatic results. This position-dependent enzymatic cleavage property might be attributed to the phosphate backbone distortion caused by the switch from C2'-endo to C3'-endo sugar pucker conformation, and was interpreted on the basis of the DNA-EcoRI structure. These 2'-modified nucleotides could behave as a regulatory element to modulate the enzymatic activity in vitro, and this property will have potential applications in genetic engineering and biomedicine.

  7. Synthesis, characterization, and photoactivated DNA cleavage by copper (II)/cobalt (II) mediated macrocyclic complexes. (United States)

    Naik, H R Prakash; Naik, H S Bhojya; Aravinda, T; Lamani, D S


    We report the synthesis of new photonuclease consisting of two Co(II)/Cu(II) complexes of macrocyclic fused quinoline. Metal complexes are [MLX(2)], type where M = Co(II) (5), Cu(II) (6), and X = Cl, and are well characterized by elemental analysis, Fourier transform infrared spectroscopy, (1)H-NMR and electronic spectra. We have shown that photocleavage of plasmid DNA is markedly enhanced when this ligand is irradiated in the presence of Cu(II), and more so than that of cobalt. The chemistry of ternary and binary Co(II) complexes showing efficient light induced (360 nm) DNA cleavage activity is summarized. The role of the metal in photoinduced DNA cleavage reactions is explored by designing complex molecules having macrocyclic structure. The mechanistic pathways are found to be concentration dependent on Co(II)/Cu(II) complexes and the photoexcitation energy photoredox chemistry. Highly effective DNA cleavage ability of 6 is attributed to the effective cooperation of the metal moiety.

  8. Yeast SREBP cleavage activation requires the Golgi Dsc E3 ligase complex. (United States)

    Stewart, Emerson V; Nwosu, Christine C; Tong, Zongtian; Roguev, Assen; Cummins, Timothy D; Kim, Dong-Uk; Hayles, Jacqueline; Park, Han-Oh; Hoe, Kwang-Lae; Powell, David W; Krogan, Nevan J; Espenshade, Peter J


    Mammalian lipid homeostasis requires proteolytic activation of membrane-bound sterol regulatory element binding protein (SREBP) transcription factors through sequential action of the Golgi Site-1 and Site-2 proteases. Here we report that while SREBP function is conserved in fungi, fission yeast employs a different mechanism for SREBP cleavage. Using genetics and biochemistry, we identified four genes defective for SREBP cleavage, dsc1-4, encoding components of a transmembrane Golgi E3 ligase complex with structural homology to the Hrd1 E3 ligase complex involved in endoplasmic reticulum-associated degradation. The Dsc complex binds SREBP and cleavage requires components of the ubiquitin-proteasome pathway: the E2-conjugating enzyme Ubc4, the Dsc1 RING E3 ligase, and the proteasome. dsc mutants display conserved aggravating genetic interactions with components of the multivesicular body pathway in fission yeast and budding yeast, which lacks SREBP. Together, these data suggest that the Golgi Dsc E3 ligase complex functions in a post-ER pathway for protein degradation.

  9. Foot-and-mouth disease virus leader proteinase: structural insights into the mechanism of intermolecular cleavage. (United States)

    Steinberger, Jutta; Grishkovskaya, Irina; Cencic, Regina; Juliano, Luiz; Juliano, Maria A; Skern, Tim


    Translation of foot-and-mouth disease virus RNA initiates at one of two start codons leading to the synthesis of two forms of leader proteinase L(pro) (Lab(pro) and Lb(pro)). These forms free themselves from the viral polyprotein by intra- and intermolecular self-processing and subsequently cleave the cellular eukaryotic initiation factor (eIF) 4 G. During infection, Lb(pro) removes six residues from its own C-terminus, generating sLb(pro). We present the structure of sLb(pro) bound to the inhibitor E64-R-P-NH2, illustrating how sLb(pro) can cleave between Lys/Gly and Gly/Arg pairs. In intermolecular cleavage on polyprotein substrates, Lb(pro) was unaffected by P1 or P1' substitutions and processed a substrate containing nine eIF4GI cleavage site residues whereas sLb(pro) failed to cleave the eIF4GI containing substrate and cleaved appreciably more slowly on mutated substrates. Introduction of 70 eIF4GI residues bearing the Lb(pro) binding site restored cleavage. These data imply that Lb(pro) and sLb(pro) may have different functions in infected cells.

  10. Enantioselective epoxidation and carbon-carbon bond cleavage catalyzed by Coprinus cinereus peroxidase and myeloperoxidase. (United States)

    Tuynman, A; Spelberg, J L; Kooter, I M; Schoemaker, H E; Wever, R


    We demonstrate that myeloperoxidase (MPO) and Coprinus cinereus peroxidase (CiP) catalyze the enantioselective epoxidation of styrene and a number of substituted derivatives with a reasonable enantiomeric excess (up to 80%) and in a moderate yield. Three major differences with respect to the chloroperoxidase from Caldariomyces fumago (CPO) are observed in the reactivity of MPO and CiP toward styrene derivatives. First, in contrast to CPO, MPO and CiP produced the (S)-isomers of the epoxides in enantiomeric excess. Second, for MPO and CiP the H(2)O(2) had to be added very slowly (10 eq in 16 h) to prevent accumulation of catalytically inactive enzyme intermediates. Under these conditions, CPO hardly showed any epoxidizing activity; only with a high influx of H(2)O(2) (300 eq in 1.6 h) was epoxidation observed. Third, both MPO and CiP formed significant amounts of (substituted) benzaldehydes as side products as a consequence of C-alpha-C-beta bond cleavage of the styrene derivatives, whereas for CPO and cytochrome c peroxidase this activity is not observed. C-alpha-C-beta cleavage was the most prominent reaction catalyzed by CiP, whereas with MPO the relative amount of epoxide formed was higher. This is the first report of peroxidases catalyzing both epoxidation reactions and carbon-carbon bond cleavage. The results are discussed in terms of mechanisms involving ferryl oxygen transfer and electron transfer, respectively.

  11. Trichomonas vaginalis metalloproteinase induces mTOR cleavage of SiHa cells. (United States)

    Quan, Juan-Hua; Choi, In-Wook; Yang, Jung-Bo; Zhou, Wei; Cha, Guang-Ho; Zhou, Yu; Ryu, Jae-Sook; Lee, Young-Ha


    Trichomonas vaginalis secretes a number of proteases which are suspected to be the cause of pathogenesis; however, little is understood how they manipulate host cells. The mammalian target of rapamycin (mTOR) regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and transcription. We detected various types of metalloproteinases including GP63 protein from T. vaginalis trophozoites, and T. vaginalis GP63 metalloproteinase was confirmed by sequencing and western blot. When SiHa cells were stimulated with live T. vaginalis, T. vaginalis excretory-secretory products (ESP) or T. vaginalis lysate, live T. vaginalis and T. vaginalis ESP induced the mTOR cleavage in both time- and parasite load-dependent manner, but T. vaginalis lysate did not. Pretreatment of T. vaginalis with a metalloproteinase inhibitor, 1,10-phenanthroline, completely disappeared the mTOR cleavage in SiHa cells. Collectively, T. vaginalis metallopeptidase induces host cell mTOR cleavage, which may be related to survival of the parasite.

  12. Exploring Regioselective Bond Cleavage and Cross-Coupling Reactions using a Low-Valent Nickel Complex. (United States)

    Desnoyer, Addison N; Friese, Florian W; Chiu, Weiling; Drover, Marcus W; Patrick, Brian O; Love, Jennifer A


    Recently, esters have received much attention as transmetalation partners for cross-coupling reactions. Herein, we report a systematic study of the reactivity of a series of esters and thioesters with [{(dtbpe)Ni}2(μ-η(2):η(2)-C6H6)] (dtbpe=1,2-bis(di-tert-butyl)phosphinoethane), which is a source of (dtbpe)nickel(0). Trifluoromethylthioesters were found to form η(2)-carbonyl complexes. In contrast, acetylthioesters underwent rapid Cacyl-S bond cleavage followed by decarbonylation to generate methylnickel complexes. This decarbonylation could be pushed backwards by the addition of CO, allowing for regeneration of the thioester. Most of the thioester complexes were found to undergo stoichiometric cross-coupling with phenylboronic acid to yield sulfides. While ethyl trifluoroacetate was also found to form an η(2)-carbonyl complex, phenyl esters were found to predominantly undergo Caryl-O bond cleavage to yield arylnickel complexes. These could also undergo transmetalation to yield biaryls. Attempts to render the reactions catalytic were hindered by ligand scrambling to yield nickel bis(acetate) complexes, the formation of which was supported by independent syntheses. Finally, 2-naphthyl acetate was also found to undergo clean Caryl-O bond cleavage, and although stoichiometric cross-coupling with phenylboronic acid proceeded with good yield, catalytic turnover has so far proven elusive.

  13. ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site. (United States)

    Abbruzzese, Genevieve; Becker, Sarah F; Kashef, Jubin; Alfandari, Dominique


    The cranial neural crest (CNC) is a highly motile population of cells that is responsible for forming the face and jaw in all vertebrates and perturbing their migration can lead to craniofacial birth defects. Cell motility requires a dynamic modification of cell-cell and cell-matrix adhesion. In the CNC, cleavage of the cell adhesion molecule cadherin-11 by ADAM13 is essential for cell migration. This cleavage generates a shed extracellular fragment of cadherin-11 (EC1-3) that possesses pro-migratory activity via an unknown mechanism. Cadherin-11 plays an important role in modulating contact inhibition of locomotion (CIL) in the CNC to regulate directional cell migration. Here, we show that while the integral cadherin-11 requires the homophilic binding site to promote CNC migration in vivo, the EC1-3 fragment does not. In addition, we show that increased ADAM13 activity or expression of the EC1-3 fragment increases CNC invasiveness in vitro and blocks the repulsive CIL response in colliding cells. This activity requires the presence of an intact homophilic binding site on the EC1-3 suggesting that the cleavage fragment may function as a competitive inhibitor of cadherin-11 adhesion in CIL but not to promote cell migration in vivo.

  14. Genetic insight of the H5N1 hemagglutinin cleavage site

    Institute of Scientific and Technical Information of China (English)


    The cleavability of the hemagglutinin (HA) plays a major role in virulence of avian influenza viruses. Detailed analyses of the cleavage sequences and their evolution would give insights into the high pathogenicity of the H5N1 virus. HA segments were visually identifiable in the cellular automata (CA) image, and a feature gene segment (FGS) was only found in H5N1 rather than any other subtype. This FGS is a 30-bp gene segment mainly consisting of 'A' and 'G'. When translated into amino acids the FGS converted into a sequence of mainly basic amino acids with positive charges. This feature amino acid segment (FAAS) was located in the cleavage site loop of HA which was potentially cleavable by various proteases. The 3D structure of H5N1 HA was reconstructed using homology modelling. It was found that the cleavage site loop was well exposed to potential proteases. The molecular surfaces were reconstructed to study how mutation and deletion of some amino acids in the FAAS affected the charge distribution. It was found that some mutations had severely changed the landscape of the charge distribution. Statistical analyses of FAAS were made with respect to when and where the H5N1 viruses were found. In 2005, there were less un-mutated FAAS than the other years according to temporal evolution, and more mutated FAAS appeared in China than other regions according to geographic distribution. These results are helpful for exploring the evolution of virus high pathogenicity.

  15. Mutation in spike protein cleavage site and pathogenesis of feline coronavirus. (United States)

    Licitra, Beth N; Millet, Jean K; Regan, Andrew D; Hamilton, Brian S; Rinaldi, Vera D; Duhamel, Gerald E; Whittaker, Gary R


    Feline coronaviruses (FCoV) exist as 2 biotypes: feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV). FECV causes subclinical infections; FIPV causes feline infectious peritonitis (FIP), a systemic and fatal disease. It is thought that mutations in FECV enable infection of macrophages, causing FIP. However, the molecular basis for this biotype switch is unknown. We examined a furin cleavage site in the region between receptor-binding (S1) and fusion (S2) domains of the spike of serotype 1 FCoV. FECV sequences were compared with FIPV sequences. All FECVs had a conserved furin cleavage motif. For FIPV, there was a correlation with the disease and >1 substitution in the S1/S2 motif. Fluorogenic peptide assays confirmed that the substitutions modulate furin cleavage. We document a functionally relevant S1/S2 mutation that arises when FIP develops in a cat. These insights into FIP pathogenesis may be useful in development of diagnostic, prevention, and treatment measures against coronaviruses.

  16. The effects of proteasome inhibitor lactacystin on mouse oocyte meiosis and first cleavage

    Institute of Scientific and Technical Information of China (English)

    TAN Xin; PENG An; WANG Yongchao; TANG Zuoqing


    In order to study the effects of ubiquitin-proteasome pathway (UPP) on mouse oocyte meiosis and cleavage, oocytes undergoing maturation and parthenogenetic activation and 1-cell embryos were treated with lactacystin, a specific inhibitor of proteasome. The results indicared that the rate of GVBD was not influenced by the treatment, but polar body extrusion, parthenogenesis and first cleavage were inhibited. Immunofluorescent staining using anti β-tubulin antibody indicated that the continuous treatment of lactacystin from GV stage disorganized microtubules and spindle assembly. When metaphase stage oocytes were treated with the drug,the already formed spindle structure was not affected, but the oocytes were arrested at metaphases. The 1-cell embryos were arrested at interphase or metaphase of first mitosis when they were incubated in the drug. Proteasome regulatory subunit PA700 was located in the spindle region, as indicated by immunofluorescence. These results suggest that UPP has effects on the process of oocyte meiosis and early cleavage in many aspects, including normal organization of spindle at prophase and segregation of chromosomes at anaphase for normal meiosis.

  17. In vitro proteolytic cleavage of Gazdar murine sarcoma virus p65gag. (United States)

    Maxwell, S; Arlinghaus, R B


    Moloney murine leukemia virus, disrupted in concentrations of 0.1 to 0.5% Nonidet P-40, catalyzed the cleavage of p65, the gag gene polyprotein of the Gazdar strain of murine sarcoma virus, into polypeptides with sizes and antigenic determinants of murine leukemia virus-specified p30, p15, pp12, and p10. Cleavage performed in the presence of 0.15% Nonidet P-40 in water yielded polypeptides of approximately 40,000 (P40) and 25,000 (P25) Mr. In vitro cleavage performed in a buffered solution containing dithiothreitol in addition to 0.1% Nonidet P-40 allowed the efficient processing of P40 to p30 and a band migrating with p10. Immunoprecipitation with monospecific sera indicated that P40 contained p30 and p10, whereas P25 contained p15 and pp12 determinants. P40 and P25 are similar in size and antigenic properties to Pr40gag and Pr25gag observed in infected cells (Naso et al, J. Virol. 32:187-198, 1979).

  18. Cleavage of CXCR1 on neutrophils disables bacterial killing in cystic fibrosis lung disease. (United States)

    Hartl, Dominik; Latzin, Philipp; Hordijk, Peter; Marcos, Veronica; Rudolph, Carsten; Woischnik, Markus; Krauss-Etschmann, Susanne; Koller, Barbara; Reinhardt, Dietrich; Roscher, Adelbert A; Roos, Dirk; Griese, Matthias


    Interleukin-8 (IL-8) activates neutrophils via the chemokine receptors CXCR1 and CXCR2. However, the airways of individuals with cystic fibrosis are frequently colonized by bacterial pathogens, despite the presence of large numbers of neutrophils and IL-8. Here we show that IL-8 promotes bacterial killing by neutrophils through CXCR1 but not CXCR2. Unopposed proteolytic activity in the airways of individuals with cystic fibrosis cleaved CXCR1 on neutrophils and disabled their bacterial-killing capacity. These effects were protease concentration-dependent and also occurred to a lesser extent in individuals with chronic obstructive pulmonary disease. Receptor cleavage induced the release of glycosylated CXCR1 fragments that were capable of stimulating IL-8 production in bronchial epithelial cells via Toll-like receptor 2. In vivo inhibition of proteases by inhalation of alpha1-antitrypsin restored CXCR1 expression and improved bacterial killing in individuals with cystic fibrosis. The cleavage of CXCR1, the functional consequences of its cleavage, and the identification of soluble CXCR1 fragments that behave as bioactive components represent a new pathophysiologic mechanism in cystic fibrosis and other chronic lung diseases.

  19. Substrate promiscuity of RdCCD1, a carotenoid cleavage oxygenase from Rosa damascena. (United States)

    Huang, Fong-Chin; Horváth, Györgyi; Molnár, Péter; Turcsi, Erika; Deli, József; Schrader, Jens; Sandmann, Gerhard; Schmidt, Holger; Schwab, Wilfried


    Several of the key flavor compounds in rose essential oil are C(13)-norisoprenoids, such as beta-damascenone, beta-damascone, and beta-ionone which are derived from carotenoid degradation. To search for genes putatively responsible for the cleavage of carotenoids, cloning of carotenoid cleavage (di-)oxygenase (CCD) genes from Rosa damascena was carried out by a degenerate primer approach and yielded a full-length cDNA (RdCCD1). The RdCCD1 gene was expressed in Escherichia coli and recombinant protein was assayed for its cleavage activity with a multitude of carotenoid substrates. The RdCCD1 protein was able to cleave a variety of carotenoids at the 9-10 and 9'-10' positions to produce a C(14) dialdehyde and two C(13) products, which vary depending on the carotenoid substrates. RdCCD1 could also cleave lycopene at the 5-6 and 5'-6' positions to produce 6-methyl-5-hepten-2-one. Expression of RdCCD1 was studied by real-time PCR in different tissues of rose. The RdCCD1 transcript was present predominantly in rose flower, where high levels of volatile C(13)-norisoprenoids are produced. Thus, the accumulation of C(13)-norisoprenoids in rose flower is correlated to the expression of RdCCD1.

  20. Ternary complexes of cobalt cysteinylglycine with histidylserine and histidylphenylalanine-stabilities and DNA cleavage properties

    Indian Academy of Sciences (India)

    Pulimamidi R Reddy; Pallerla Manjula


    Interaction of cobalt cysteinylglycine with histidylserine and histidylphenylalanine was investigated in a 1 : 1 : 1 ratio at 35°C and 0.10 mol dm-3 ionic strength. Their stabilities and geometries were determined. Their DNA binding and cleavage properties were investigated. The intrinsic binding constants () for DNA bound 1 and 2 (3.03 × 103 M-1 for 1 and 3.87 × 103 M-1 for 2) were determined. Even though the negative charge on the complexes reduced their affinity for DNA, there was an enhancement of binding through specificity. The degradation of plasmid DNA was achieved by cobalt dipeptide complexes [CoII(CysGly)(HisSer)] (1) and [CoII(CysGly)(HisPhe)] (2). Cleavage experiments revealed that 1 and 2 cleave supercoiled DNA (form I) to nicked circular (form II) through hydrolytic pathway at physiological H. The DNA hydrolytic cleavage rate constants for complexes 1 and 2 were determined to be 0.62 h-1, for 1 and 0.38 h-1 for 2 respectively.

  1. Structural Basis for Accelerated Cleavage of Bovine Pancreatic Trypsin Inhibitor (BPTI) by Human Mesotrypsin

    Energy Technology Data Exchange (ETDEWEB)

    Salameh,M.; Soares, A.; Hockla, A.; Radisky, E.


    Human mesotrypsin is an isoform of trypsin that displays unusual resistance to polypeptide trypsin inhibitors and has been observed to cleave several such inhibitors as substrates. Whereas substitution of arginine for the highly conserved glycine 193 in the trypsin active site has been implicated as a critical factor in the inhibitor resistance of mesotrypsin, how this substitution leads to accelerated inhibitor cleavage is not clear. Bovine pancreatic trypsin inhibitor (BPTI) forms an extremely stable and cleavage-resistant complex with trypsin, and thus provides a rigorous challenge of mesotrypsin catalytic activity toward polypeptide inhibitors. Here, we report kinetic constants for mesotrypsin and the highly homologous (but inhibitor sensitive) human cationic trypsin, describing inhibition by, and cleavage of BPTI, as well as crystal structures of the mesotrypsin-BPTI and human cationic trypsin-BPTI complexes. We find that mesotrypsin cleaves BPTI with a rate constant accelerated 350-fold over that of human cationic trypsin and 150,000-fold over that of bovine trypsin. From the crystal structures, we see that small conformational adjustments limited to several side chains enable mesotrypsin-BPTI complex formation, surmounting the predicted steric clash introduced by Arg-193. Our results show that the mesotrypsin-BPTI interface favors catalysis through (a) electrostatic repulsion between the closely spaced mesotrypsin Arg-193 and BPTI Arg-17, and (b) elimination of two hydrogen bonds between the enzyme and the amine leaving group portion of BPTI. Our model predicts that these deleterious interactions accelerate leaving group dissociation and deacylation.

  2. The DNA cleavage reaction of topoisomerase II: wolf in sheep's clothing. (United States)

    Deweese, Joseph E; Osheroff, Neil


    Topoisomerase II is an essential enzyme that is required for virtually every process that requires movement of DNA within the nucleus or the opening of the double helix. This enzyme helps to regulate DNA under- and overwinding and removes knots and tangles from the genetic material. In order to carry out its critical physiological functions, topoisomerase II generates transient double-stranded breaks in DNA. Consequently, while necessary for cell survival, the enzyme also has the capacity to fragment the genome. The DNA cleavage/ligation reaction of topoisomerase II is the target for some of the most successful anticancer drugs currently in clinical use. However, this same reaction also is believed to trigger chromosomal translocations that are associated with specific types of leukemia. This article will familiarize the reader with the DNA cleavage/ligation reaction of topoisomerase II and other aspects of its catalytic cycle. In addition, it will discuss the interaction of the enzyme with anticancer drugs and the mechanisms by which these agents increase levels of topoisomerase II-generated DNA strand breaks. Finally, it will describe dietary and environmental agents that enhance DNA cleavage mediated by the enzyme.

  3. Natural thermal convection in fractured porous media (United States)

    Adler, P. M.; Mezon, C.; Mourzenko, V.; Thovert, J. F.; Antoine, R.; Finizola, A.


    In the crust, fractures/faults can provide preferential pathways for fluid flow or act as barriers preventing the flow across these structures. In hydrothermal systems (usually found in fractured rock masses), these discontinuities may play a critical role at various scales, controlling fluid flows and heat transfer. The thermal convection is numerically computed in 3D fluid satured fractured porous media. Fractures are inserted as discrete objects, randomly distributed over a damaged volume, which is a fraction of the total volume. The fluid is assumed to satisfy Darcy's law in the fractures and in the porous medium with exchanges between them. All simulations were made for Rayleigh numbers (Ra) equilibrium with the medium), cubic boxes and closed-top conditions. Checks were performed on an unfractured porous medium and the convection cells do start for the theoretical value of Ra, namely 4p². 2D convection was verified up to Ra=800. The influence of parameters such as fracture aperture (or fracture transmissivity), fracture density and fracture length is studied. Moreover, these models are compared to porous media with the same macroscopic permeability. Preliminary results show that the non-uniqueness associated with initial conditions which makes possible either 2D or 3D convection in porous media (Schubert & Straus 1979) is no longer true for fractured porous media (at least for 50fracture density and fracture aperture on the Nusselt number (Nu) is highly Ra dependent. The effect of the damaged zone on Nu is roughly proportional to its size. All these models also allows us to determine for which range of fracture density the fractured porous medium is in good agreement with an unfractured porous medium of the same bulk permeability.

  4. Vertebral Geometry Parameters Can Predict Fractures

    Directory of Open Access Journals (Sweden)

    P Tofighi


    Full Text Available Background: The aim of this study was to investigate vertebral geometry changes and determine cutoff value of vertebral height to predict fractures. Methods: In a cross-sectional study, 280 postmenopausal women recruited .In all subjects bone mineral density and radiog¬raphy of the lumbar spine performed. Lateral radiographs were evaluated for identification of vertebral fractures, using a validated semiquantitative method. T-score of vertebral height was calculated based on data extracted from Iranian Multi¬center Osteoporosis Study. ROC curve used to determine cut off value of vertebral height T-score to predict fractures. Results: The mean of age and BMI were 55.34±8.7 years and 27.73±5 kg/m2, respectively. Among osteoporotic women, 59.8% had one or more vertebral fractures and 23.8% had at least 2 fractures. In fracture group the T-score of spine and femur BMD was lower than the others. The mean of vertebral height in women without fractures was 12.94±0.6 cm, and in the patient with 4 or more fractures was12.3, thus every fracture accompany with 1.2% decreases in the height of vertebrae. The prevalence of vertebral fracture in osteoporotic patients was 71.4% and in healthy cases 39.5%. Better estimation of vertebral height T score in ROC curve was less than -0.7.The sensitivity and specificity of the cut off value were 81.3% and 52.9%, respectively. Conclusion: Vertebral fractures are common fractures in postmenopausal women. There was a correlation between verte¬bral height and fractures. Vertebral geometric parameters especially height T score can be used for fracture screening.

  5. Hydraulic fracturing model based on the discrete fracture model and the generalized J integral (United States)

    Liu, Z. Q.; Liu, Z. F.; Wang, X. H.; Zeng, B.


    The hydraulic fracturing technique is an effective stimulation for low permeability reservoirs. In fracturing models, one key point is to accurately calculate the flux across the fracture surface and the stress intensity factor. To achieve high precision, the discrete fracture model is recommended to calculate the flux. Using the generalized J integral, the present work obtains an accurate simulation of the stress intensity factor. Based on the above factors, an alternative hydraulic fracturing model is presented. Examples are included to demonstrate the reliability of the proposed model and its ability to model the fracture propagation. Subsequently, the model is used to describe the relationship between the geometry of the fracture and the fracturing equipment parameters. The numerical results indicate that the working pressure and the pump power will significantly influence the fracturing process.

  6. An Unusual Combination of Acetabular and Pelvic Fracture: Is This a New Subtype of Acetabular Fracture?

    Directory of Open Access Journals (Sweden)

    Reza Tavakoli Darestani


    Full Text Available Introduction: Acetabular fractures are a common problem among young males. An acetabular fracture with disruption of the joint surface, if untreated, will rapidly lead to post-traumatic osteoarthritis. Proper reduction and internal fixation depend on accurate classification and the quality of imaging.Case Presentation: We present an unusual form of acetabular fracture, which is not included in the conventional classification (Judet and Letournel ; this occurred in a middle-aged male who was operatively treated without any complications. In this case due to posterior extension of the fracture into the SI joint and concomitant anterior column fracture in the area above the acetabular dome, no portion of the acetabular anterior surface remained connected to the innominate bone.Conclusions: We recognized this type of fracture and treated it similarly to both column fractures. We recommend that the classification of acetabular fractures be modified to include this type of fracture.

  7. Rubber oxygenase and latex clearing protein cleave rubber to different products and use different cleavage mechanisms. (United States)

    Birke, Jakob; Jendrossek, Dieter


    Two types of enzyme for oxidative cleavage of poly(cis-1,4-isoprene) are known. One is rubber oxygenase (RoxA) that is secreted by Xanthomonas sp. strain 35Y and a few other Gram-negative rubber-degrading bacteria during growth on polyisoprene. RoxA was studied in the past, and the recently solved structure showed a structural relationship to bacterial cytochrome c peroxidases (J. Seidel et al., Proc. Natl. Acad. Sci. U. S. A. 110:13833-13838, 2013, The other enzyme is latex-clearing protein (Lcp) that is secreted by rubber-degrading actinomycetes, but Lcp has not yet been purified. Here, we expressed Lcp of Streptomyces sp. strain K30 in a ΔroxA background of Xanthomonas sp. strain 35Y and purified native (untagged) Lcp. The specific activities of Lcp and RoxA were 0.70 and 0.48 U/mg, respectively. Lcp differed from RoxA in the absence of heme groups and other characteristics. Notably, Lcp degraded polyisoprene via endo-type cleavage to tetra-C20 and higher oligo-isoprenoids with aldehyde and keto end groups, whereas RoxA used an exo-type cleavage mechanism to give the main end product 12-oxo-4,8-dimethyltrideca-4,8-diene-1-al (ODTD). RoxA was able to cleave isolated Lcp-derived oligo-isoprenoid molecules to ODTD. Inhibitor studies, spectroscopic investigations and metal analysis gave no indication for the presence of iron, other metals, or cofactors in Lcp. Our results suggest that Lcp could be a member of the growing group of cofactor-independent oxygenases and differs in the cleavage mechanism from heme-dependent RoxA. In conclusion, RoxA and Lcp represent two different answers to the same biochemical problem, the cleavage of polyisoprene, a polymer that has carbon-carbon double bonds as the only functional groups for enzymatic attack.

  8. Atomistic study on mixed-mode fracture mechanisms of ferrite iron interacting with coherent copper and nickel nanoclusters (United States)

    Al-Motasem, Ahmed Tamer; Mai, Nghia Trong; Choi, Seung Tae; Posselt, Matthias


    The effect of copper and/or nickel nanoclusters, generally formed by neutron irradiation, on fracture mechanisms of ferrite iron was investigated by using molecular statics simulation. The equilibrium configuration of nanoclusters was obtained by using a combination of an on-lattice annealing based on Metropolis Monte Carlo method and an off-lattice relaxation by molecular dynamics simulation. Residual stress distributions near the nanoclusters were also calculated, since compressive or tensile residual stresses may retard or accelerate, respectively, the propagation of a crack running into a nanocluster. One of the nanoclusters was located in front of a straight crack in ferrite iron with a body-centered cubic crystal structure. Two crystallographic directions, of which the crack plane and crack front direction are (010)[001] and (111) [ 1 bar 10 ] , were considered, representing cleavage and non-cleavage orientations in ferrite iron, respectively. Displacements corresponding to pure opening-mode and mixed-mode loadings were imposed on the boundary region and the energy minimization was performed. It was observed that the fracture mechanisms of ferrite iron under the pure opening-mode loading are strongly influenced by the presence of nanoclusters, while under the mixed-mode loading the nanoclusters have no significant effect on the crack propagation behavior of ferrite iron.

  9. Acquisition of a novel eleven amino acid insertion directly N-terminal to a tetrabasic cleavage site confers intracellular cleavage of an H7N7 influenza virus hemagglutinin

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, Brian S.; Sun, Xiangjie; Chung, Changik [Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca NY 14853 (United States); New York Center of Excellence for Influenza Research and Surveillance, University of Rochester Medical Center, Rochester NY 14627 (United States); Whittaker, Gary R., E-mail: [Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca NY 14853 (United States); New York Center of Excellence for Influenza Research and Surveillance, University of Rochester Medical Center, Rochester NY 14627 (United States)


    A critical feature of highly pathogenic avian influenza viruses (H5N1 and H7N7) is the efficient intracellular cleavage of the hemagglutinin (HA) protein. H7N7 viruses also exist in equine species, and a unique feature of the equine H7N7 HA is the presence of an eleven amino acid insertion directly N-terminal to a tetrabasic cleavage site. Here, we show that three histidine residues within the unique insertion of the equine H7N7 HA are essential for intracellular cleavage. An asparagine residue within the insertion-derived glycosylation site was also found to be essential for intracellular cleavage. The presence of the histidine residues also appear to be involved in triggering fusion, since mutation of the histidine residues resulted in a destabilizing effect. Importantly, the addition of a tetrabasic site and the eleven amino acid insertion conferred efficient intracellular cleavage to the HA of an H7N3 low pathogenicity avian influenza virus. Our studies show that acquisition of the eleven amino acid insertion offers an alternative mechanism for intracellular cleavage of influenza HA.

  10. Enhanced cleavage of double-stranded DNA by artificial zinc-finger nuclease sandwiched between two zinc-finger proteins. (United States)

    Mineta, Yusuke; Okamoto, Tomoyuki; Takenaka, Kosuke; Doi, Norio; Aoyama, Yasuhiro; Sera, Takashi


    To enhance DNA cleavage by zinc-finger nucleases (ZFNs), we sandwiched a DNA cleavage enzyme with two artificial zinc-finger proteins (AZPs). Because the DNA between the two AZP-binding sites is cleaved, the AZP-sandwiched nuclease is expected to bind preferentially to a DNA substrate rather than to cleavage products and thereby cleave it with multiple turnovers. To demonstrate the concept, we sandwiched a staphylococcal nuclease (SNase), which cleaves DNA as a monomer, between two three-finger AZPs. The AZP-sandwiched SNase cleaved large amounts of dsDNA site-specifically. Such multiple-turnover cleavage was not observed with nucleases that possess a single AZP. Thus, AZP-sandwiched nucleases will further refine ZFN technology.

  11. Dienone-phenol Rearrangement of C-9 Oxygenated Decalinic Dienone and Analogs through B-Ring Cleavage

    Institute of Scientific and Technical Information of China (English)


    Dehydrogenation of 9-hydroxy decalinic enones and analogs with DDQ resulted in a formal dienone-phenol type rearrangement via B-ring cleavage, while the corresponding dienone acetates underwent base-catalyzed formal dienone-phenol type rearrangement analogously.

  12. The healing of fractured bones

    Energy Technology Data Exchange (ETDEWEB)

    Bacon, G.E. [Central Electricity Generating Board, Cheltenham (United Kingdom)


    A method utilising neutron beams of width 1 mm, used on D1B (2.4 A) and D20 (1.3 A) to study the healing of fractured bones is presented. It is found that the callus bone uniting the fractured tibia of a sheep, whose healing had been encouraged by daily mechanical vibration over a period of three months, showed no trace of the large preferential vertical orientation of the apatite crystals which is characteristic of the normal bone. Nevertheless the bone had regained about 60% of its mechanical strength and the callus bone, although not oriented, was well crystallized. It is considered that the new monochromator for D20, expected to give increased intensity at 2.5 A, will be of considerable advantage. (author). 2 refs.

  13. Buttress plating for a rare case of comminuted medial condylar Hoffa fracture associated with patellar fracture

    Institute of Scientific and Technical Information of China (English)

    Ashwani Soni; Ramesh K Sen; Uttam Chand Saini; Dajjit Singh; Sushil Chaudhary


    Hoffa fracture is an uncommon injury.In the literature,lateral condylar Hoffa fracture is mentioned as a more common injury pattern than medial condylar Hoffa fracture.The mechanism of injury and method of treatment is not very well described in the literature.We are presenting a rare case of comminuted medial condylar Hoffa fracture with ipsitateral patellar fracture.The mechanism of injury has not been described in the literature.Lag screw fixation,which is the most acceptable method of treatment,is not possible due to comminution.We explain the possible mechanism of injury and fix the fracture with L-buttress plate.

  14. Our Results in Penile Fractures

    Directory of Open Access Journals (Sweden)

    Tufan Süelözgen


    Full Text Available Introduction Penile fracture is a urological emergency caused by direct trauma to an erected penis, tearing the tunica albuginea in the corpus cavernosum. The preferred treatment method is draining the hematoma and surgical repair of tunica albuginea tear as soon as possible following diagnosis. Materials and Methods Forty-nine patients who were diagnosed with penile fracture between January 2009 and December 2014 were reviewed. Physical examination was performed to see the extent of penile hematoma, the side of the penile curvature and the presence of blood in the external meatus. Two patients who were diagnosed with urethrorrhagia underwent retrograde urethrogram for urethral injury. In all patients, penile skin was peeled using a circular subcoronal degloving incision and tunica tear was repaired using absorbable suture materials. The patients were then followed for painful erections, penile deformities and erection angles. Results The average age of the 49 patients, who were included in the study, was 36.5 years (21-65. In their etiological questioning, most patients reported the fracture occurring during sexual intercourse. Retrograde urethrography was indicated in 2 patients with blood in the external meatus and were diagnosed with urethral injury. The patients were taken to emergency surgery. Tunica defects varied between 1 and 2 cm. Incomplete urethral injuries were primarily repaired around 18 French Foley catheter. None of the patients reported penile deformity or painful erections. Their erection angles were found to be within the normal range. Conclusion Even though it is a relatively rare condition, penile fractures are so important that might cause serious complications when not treated surgically. A thorough anamnesis and physical examination suffice for diagnosis.

  15. Drawing Brittle Fracture Causes Analysis of Large Gauge High Carbon Steel 82B Wire Rod%大规格高碳硬线82B拉拔脆断原因分析

    Institute of Scientific and Technical Information of China (English)

    张寄东; 智建国; 吕刚; 宿成


    采用金相组织检验分析等方法,分析了大规格82B拉拔劈裂脆断问题.结果表明:劈裂断口试样的中心处,由于锰、铬偏析而出现异常的马氏体组织,导致其变形与基体不一致,在拉拔过程中中心马氏体断裂成为裂纹源.断口附近表面存在结疤和擦伤等表面缺陷,中心马氏体和表面缺陷共同导致大规格82B拉拔劈裂脆断.通过优化合金元素锰、铬的成分含量,同时改善炼钢、轧制、拉拔等工艺,有效地降低了劈裂脆断的发生率.%The causes of drawing cleavage brittle fracture of large gauge high carbon steel 82B wire rod are analyzed by carrying out metallographic structure inspection and analysis. They are found out as the result of Mn, Cr central segregation causing formation of martensite in the centre of the wire rod, and the center martensite fracture becomes one of the sources of crack in the process of drawing because of the difference of deformation rate between the central part and the other area. There are some defects of scar and scratches near the fracture surface. It is manifested, through deeper analyzing, the main cause of drawing cleavage brittle fracture is the combined action of central martensite and surface defect. The incidence rate of cleavage brittle fracture defect has been reduced effectively through optimizing the content of Mn and Cr and improving the technics of steelmaking, rolling and drawing.

  16. prpC-related signal transduction is influenced by copper, membrane integrity and the alpha cleavage site

    Institute of Scientific and Technical Information of China (English)

    Cathryn L Haigh; Victoria A Lewis; Laura J Vella; Colin L Masters; Andrew F Hill; Victoria A Lawson; Steven J Collins


    The copper-binding, membrane-anchored, cellular prion protein (PrPC) has two constitutive cleavage sites pro-ducing distinct N- and C-terminal fragments (N1/C1 and N2/C2). Using RKI3 cells expressing either human PrPC, mouse PrPC or mouse PrPC carrying the 3F4 epitope, this study explored the influence of the PrPC primary sequence on endoproteolytic cleavage and one putative PrPC function, MAP kinase signal transduction, in response to exoge-nous copper with or without a perturbed membrane environment. PrPC primary sequence, especially that around the N1/C1 cleavage site, appeared to influence basal levels of proteolysis at this location and extracellular signal-regulat-ed kinase 1/2 (ERK1/2) phosphorylation, with increased processing demonstrating an inverse relationship with basal ERK1/2 activation. Human PrPC showed increased N1/C1 cleavage in response to copper alone, accompanied by spe-cific p38 and JNK/SAPK phosphorylation. Combined exposure to copper plus the cholesterol-sequestering antibiotic filipin resulted in a mouse PrPC-specific substantial increase in signal protein phosphorylation, accompanied by an increase in N1/C1 cleavage. Mouse PrPC harboring the human N1/C1 cleavage site assumed more human-like profiles basally and in response to copper and altered membrane environments. Our results demonstrate that the PrPC pri-mary sequence around the N1/C1 cleavage site influences endoproteolytic processing at this location, which appears linked to MAP kinase signal transduction both basally and in response to copper. Further, the primary sequence ap-pears to confer a mutual dependence of N1/C1 cleavage and membrane integrity on the fidelity of prpC-related signal transduction in response to exogenous stimuli.

  17. Cleavage specificity analysis of six type II transmembrane serine proteases (TTSPs using PICS with proteome-derived peptide libraries.

    Directory of Open Access Journals (Sweden)

    Olivier Barré

    Full Text Available BACKGROUND: Type II transmembrane serine proteases (TTSPs are a family of cell membrane tethered serine proteases with unclear roles as their cleavage site specificities and substrate degradomes have not been fully elucidated. Indeed just 52 cleavage sites are annotated in MEROPS, the database of proteases, their substrates and inhibitors. METHODOLOGY/PRINCIPAL FINDING: To profile the active site specificities of the TTSPs, we applied Proteomic Identification of protease Cleavage Sites (PICS. Human proteome-derived database searchable peptide libraries were assayed with six human TTSPs (matriptase, matriptase-2, matriptase-3, HAT, DESC and hepsin to simultaneously determine sequence preferences on the N-terminal non-prime (P and C-terminal prime (P' sides of the scissile bond. Prime-side cleavage products were isolated following biotinylation and identified by tandem mass spectrometry. The corresponding non-prime side sequences were derived from human proteome databases using bioinformatics. Sequencing of 2,405 individual cleaved peptides allowed for the development of the family consensus protease cleavage site specificity revealing a strong specificity for arginine in the P1 position and surprisingly a lysine in P1' position. TTSP cleavage between R↓K was confirmed using synthetic peptides. By parsing through known substrates and known structures of TTSP catalytic domains, and by modeling the remainder, structural explanations for this strong specificity were derived. CONCLUSIONS: Degradomics analysis of 2,405 cleavage sites revealed a similar and characteristic TTSP family specificity at the P1 and P1' positions for arginine and lysine in unfolded peptides. The prime side is important for cleavage specificity, thus making these proteases unusual within the tryptic-enzyme class that generally has overriding non-prime side specificity.

  18. The action of the bacterial toxin microcin B17. Insight into the cleavage-religation reaction of DNA gyrase. (United States)

    Pierrat, Olivier A; Maxwell, Anthony


    We have examined the effects of the bacterial toxin microcin B17 (MccB17) on the reactions of Escherichia coli DNA gyrase. MccB17 slows down but does not completely inhibit the DNA supercoiling and relaxation reactions of gyrase. A kinetic analysis of the cleavage-religation equilibrium of gyrase was performed to determine the effect of the toxin on the forward (cleavage) and reverse (religation) reactions. A simple mechanism of two consecutive reversible reactions with a nicked DNA intermediate was used to simulate the kinetics of cleavage and religation. The action of MccB17 on the kinetics of cleavage and religation was compared with that of the quinolones ciprofloxacin and oxolinic acid. With relaxed DNA as substrate, only a small amount of gyrase cleavage complex is observed with MccB17 in the absence of ATP, whereas the presence of the nucleotide significantly enhances the effect of the toxin on both the cleavage and religation reactions. In contrast, ciprofloxacin, oxolinic acid, and Ca2+ show lesser dependence on ATP to stabilize the cleavage complex. MccB17 enhances the overall rate of DNA cleavage by increasing the forward rate constant (k2) of the second equilibrium. In contrast, ciprofloxacin increases the amount of cleaved DNA by a combined effect on the forward and reverse rate constants of both equilibria. Based on these results and on the observations that MccB17 only slowly inhibits the supercoiling and relaxation reactions, we suggest a model of the interaction of MccB17 with gyrase.

  19. Natural fracture characterization using passive seismic illumination

    Energy Technology Data Exchange (ETDEWEB)

    Nihei, K.T.


    The presence of natural fractures in reservoir rock can significantly enhance gas production, especially in tight gas formations. Any general knowledge of the existence, location, orientation, spatial density, and connectivity of natural fractures, as well as general reservoir structure, that can be obtained prior to active seismic acquisition and drilling can be exploited to identify key areas for subsequent higher resolution active seismic imaging. Current practices for estimating fracture properties before the acquisition of surface seismic data are usually based on the assumed geology and tectonics of the region, and empirical or fracture mechanics-based relationships between stratigraphic curvature and fracturing. The objective of this research is to investigate the potential of multicomponent surface sensor arrays, and passive seismic sources in the form of local earthquakes to identify and characterize potential fractured gas reservoirs located near seismically active regions. To assess the feasibility of passive seismic fracture detection and characterization, we have developed numerical codes for modeling elastic wave propagation in reservoir structures containing multiple, finite-length fractures. This article describes our efforts to determine the conditions for favorable excitation of fracture converted waves, and to develop an imaging method that can be used to locate and characterize fractures using multicomponent, passive seismic data recorded on a surface array.

  20. Current concepts in pediatric femur fracture treatment. (United States)

    Kanlic, Enes; Cruz, Miguel


    Femoral neck fractures require urgent evacuation of intracapsular hematoma, anatomic reduction, and secure fixation with screws and cast immobilization. Extracapsular trochanteric and subtrochanteric fractures are best treated by fixed angle devices (locked plates or dynamic screw and side plate). "Length stable" low energy shaft fractures with minimal displacement or fractures are treated operatively. Transverse or short oblique shaft fractures in patients fractures. Children > 12 years have less risk of vascular disturbance to the proximal physis, and should have lateral transtrochanateric entry locked rigid nails. Fractures with severe soft tissue injuries could be temporized with external fixation. Distal physis and epiphyseal injuries require anatomical reduction and smooth wires and/or screw fixation (placed in such a way as to minimize further damage to the physis) and need to be augmented with a brace. Leg-length discrepancy is not a significant clinical problem in operatively treated patients. We recommend hardware removal after complete fracture healing, usually in 6 to 12 months. Implants left in the growing child could become buried deep inside of the bone, or cause "periprosthetic" fractures and/or eventually impede adult reconstruction. Minimal risks are reported for hardware removal in healthy patients with healed fractures (4 cortices bridged).